Product Catalogue - EUROIMMUN US, Inc. · PDF file—1— EUROIMMUN Medizinische Labordiagnostika AG Product Catalogue Diagnostics for the Determination of Autoantibodies, for Infectious

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EUROIMMUNM e d i z i n i s c h eL a b o r d i a g n o s t i k aA G

Product Catalogue

Diagnostics for the Determination of Autoantibodies,

for Infectious Serology and Allergology

Indirect Immunofluorescence — ELISA — RIA — Westernblot

EUROASSAY — EUROLINE — EUROPLUS

2010

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2010

Produktkatalog2010.p65 04.11.2009, 12:401

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Table of Contents

EUROIMMUN – Company Profile .................................................................................................................................................. 3

Techniques for the Serological Investigation of Antibodies ....................................................................................................... 5Indirect Immunofluorescence: An Easy and Modern Method ............................................................................................................................... 6BIOCHIP Mosaics™ ..................................................................................................................................................................................................... 9The Indirect Immunofluorescence Test, Performed Using the TITERPLANE™ Technique.............................................................................. 10Recommended Serum Dilutions for Indirect Immunofluorescence ................................................................................................................... 12Diagnostically Relevant Systemic Autoantibodies ............................................................................................................................................... 16Organ-/Tissue-Specific Autoantibodies .................................................................................................................................................................. 17Antibodies for Infectious Serology ......................................................................................................................................................................... 18Antibodies for Allergology ....................................................................................................................................................................................... 19EUROIMMUN Microplate ELISA .............................................................................................................................................................................. 18ELISA Automation using the EUROIMMUN Analyzer I ........................................................................................................................................ 22Incubating the Microplate ELISA ............................................................................................................................................................................. 23EUROASSAY: Line Blots in TITERPLANE™Technique Format ........................................................................................................................... 24Incubating the EUROASSAY (TITERPLANE™Technique) .................................................................................................................................... 25The EUROLINE: A New Technique for Extensive Antibody Profiles .................................................................................................................. 26EUROLINE Automation Using EUROBlotMaster and EUROLineScan ................................................................................................................ 27Westernblots/EUROLINE-WB: Reliable Differentiation of Antibodies Present .................................................................................................. 28Incubating the EUROLINE/Westernblot/EUROLINE-WB ....................................................................................................................................... 29EUROIMMUN Radioimmunoassays (RIA/IRMA) ................................................................................................................................................... 30

EUROIMMUN Products for the Determination of Autoantibodies ............................................................................................ 31Autoantibodies against Cell Nuclei (ANA) ............................................................................................................................................................. 32Autoantibodies against Double-Stranded DNA (dsDNA) ..................................................................................................................................... 35Autoantibodies against CCP and Sa ....................................................................................................................................................................... 36Autoantibodies against Mitochondria (AMA) ........................................................................................................................................................ 37Autoantibodies against Liver Antigens .................................................................................................................................................................. 38Autoantibodies against Thyroid Gland Antigens / Antigen Detections ............................................................................................................. 40Autoantikörper against Antigens of the Skin ........................................................................................................................................................ 41Autoantibodies against Neuronal Antigens ........................................................................................................................................................... 42Autoantibodies against Islet Cell Antigens ............................................................................................................................................................ 44Autoantibodies against Parietal Cells (PCA) .......................................................................................................................................................... 45Autoantibodies against Granulocyte Cytoplasm (cANCA/pANCA) ..................................................................................................................... 46Antibodies against Endomysium and Gliadin ....................................................................................................................................................... 48

EUROIMMUN Products for Infectious Serology ........................................................................................................................ 49Antibodies against Borrelia ...................................................................................................................................................................................... 50Antibodies against Epstein-Barr Virus (EBV) ......................................................................................................................................................... 52Antibodies against Helicobacter Pylori .................................................................................................................................................................. 54Antibodies against Herpes Simplex Virus (HSV) .................................................................................................................................................. 55Antibodies against Chlamydia ................................................................................................................................................................................. 56Antibodies against Emerging Viruses .................................................................................................................................................................... 57BIOCHIP Mosaics™ for Infectious Serology .......................................................................................................................................................... 58Additional Reagents for the Determination of Acute Infections ......................................................................................................................... 60

EUROIMMUN Products for Allergology ..................................................................................................................................... 61

Order Information and Product Data ......................................................................................................................................... 64Fluorescence-Labelled Antibodies: Fluorescein (FITC) for EUROIMMUN IIFT .................................................................................................. 65Controls for EUROIMMUN IIFT: Organ-Specific Autoantibodies ........................................................................................................................ 66Controls for EUROIMMUN IIFT: Systemic Autoantibodies .................................................................................................................................. 68Controls for EUROIMMUN IIFT: Infectious Serology ............................................................................................................................................ 70Controls for EUROIMMUN IIFT: Determination of Further Antibodies .............................................................................................................. 76Controls for EUROIMMUN Westernblots/EUROLINE-WB .................................................................................................................................... 77EUROASSAY for the Determination of Autoantibodies (Test Systems) ............................................................................................................ 79EUROLINE for the Determination of Autoantibodies (Test Systems) ................................................................................................................ 80EUROLINE for Infectious Serology (Test Systems) .............................................................................................................................................. 81EUROLINE for Allergology (Test Systems) ............................................................................................................................................................ 81Westernblot/EUROLINE-WB for the Determination of Autoantibodies (Test Systems) ................................................................................... 83Westernblot/EUROLINE-WB for Infectious Serology (Test Systems) ................................................................................................................. 84Microplate ELISA for the Determination of Autoantibodies (Test Systems) ..................................................................................................... 86Latex Agglutination tests for the Determination of Autoantibodies (Test Systems) ....................................................................................... 89EUROArray for Molecular Genetic Determinations (Test Systems) ................................................................................................................... 89Radioimmunoassay (RIA) for the Determination of Autoantibodies / Autoantigens / Hormone Determination (Test Systems) ............... 89Microplate ELISA for Infectious Serology (Test Systems) ................................................................................................................................... 91Microplate ELISA for the Determination of Antibodies against Other Antigens (Test Systems) ................................................................... 95Allercoat™ 6 System ................................................................................................................................................................................................ 96Diagnostics for Indirect Immunofluorescence: Organ-Specific Autoantibodies ............................................................................................. 116Diagnostics for Indirect Immunofluorescence: Systemic Autoantibodies ....................................................................................................... 126Diagnostics for Indirect Immunofluorescence: Infectious Serology ................................................................................................................. 134Diagnostics for Indirect Immunofluorescence: Other Antigens ........................................................................................................................ 151Further Reagents for EUROIMMUN IIFT .............................................................................................................................................................. 151Other Items for EUROIMMUN IIFT ........................................................................................................................................................................ 152General Delivery Conditions .................................................................................................................................................................................. 153

Index ......................................................................................................................................................................................... 154


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EUROIMMUN – COMPANY PROFILE

EUROIMMUN was founded in September 1987 and today has its headquarters in Lübeck, Germany. Branchesare situated in Groß Grönau near Lübeck (Schleswig-Holstein), in Rennersdorf (Upper Lusatia, Saxony),Dassow (Mecklenburg-Western Pomerania) and in Pegnitz (Upper Franconia, Bavaria). Further EUROIMMUNsubsidiaries can be found in Canada (Mississauga), China (Beijing, Hangzhou), Great Britain (Pontypoolin Wales), Italy (Padua), Lebanon (Beirut), Poland (Wroclaw), Switzerland (Lucerne), Singapore, SouthAfrica (Capetown), Turkey (Istanbul) and the USA (New Jersey). At present EUROIMMUN has 714employees in Germany, 884 worldwide. The company is ISO-certified (EN ISO 9001:2008, EN ISO 13485:2003/CMDCAS).

EUROIMMUN produces reagents for medical laboratory diagnostics. In the foreground are test systemsfor the determination of various antibodies in patient serum in the diagnosis of autoimmune diseases,infectious diseases and allergies.

The test methods employed are predominantly indirect immunofluorescence, microplate ELISA, variousblot techniques (Westernblot, EUROASSAY, EUROLINE, EUROLINE-WB) and all molecular biologytechniques. The company is based on worldwide-patented state-of-the-art production methods andmicroanalysis techniques and is one of the world’s leading manufacturers of medical laboratory diagnostics.

The BIOCHIPs are one of EUROIMMUN’s many inventions: paper-thin sheets of glass are coated with cells ortissue sections and then cut automatically into millimetre-sized fragments which are subsequently glued ontoslides using a fully automated device. This BIOCHIP technology allows extreme miniaturization andstandardization of immunbiochemical analyses. With BIOCHIP Mosaics™made from 30 or more differentorgan sections, cell substrates or defined antigens (EUROPLUS™) only minimum incubation efforts arenecessary to obtain a detailed antibody profile.

In EUROIMMUN enzyme immunoassays (ELISA) defined antigens, purified using state-of-the-artbiotechnological processes, are employed as the antigen substrate. Some of these antigens are synthesized inthe company’s molecular biology laboratories. EUROIMMUN ELISA are characterized by their excellentstability, simple handling and short incubation times, and they are ideal for automated use. All reagents aredelivered ready-to-use and are exchangeable between different lots. EUROIMMUN offers the largest and mostdifferentiated arsenal of enzyme immunoassays worldwide for the diagnosis of autoimmune and infectiousdiseases.

Company site Groß Grönau Company headquarters Lübeck

Company branch Dassow Company branch PegnitzCompany branch Rennersdorf


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The innovative procedures EUROASSAY and EUROLINE developed by EUROIMMUN follow the same testprinciple as the ELISA methods, with the use of the BIOCHIP technology. At EUROIMMUN purified antigens areprinted in parallel lines at defined positions on membrane strips. Following incubation, users can evaluateresults visually without additional equipment. These reagents allow in particular the differentiation ofantibodies that are not clearly defined microscopically by indirect immunofluorescence. EUROASSAY andEUROLINE are also employed in laboratories where no sophisticated laboratory instruments are available.

EUROIMMUN produces an extensive range of Westernblot strip test systems and corresponding reagents forconfirmation of positive fluorescence and ELISA results as well as clarification of difficult-to-interpret results inautoimmune diagnostics, infectious serology and allergology. Refined electrophoretical processes have beendeveloped to allow the precise separation of diagnostically relevant proteins from one another. Lot-specificevaluation templates are produced for the evaluation of band patterns. The program ”EUROLineScan“enables fully automated evaluation of membrane-based test systems and simplifies the archiving of resultswith large sample series.

One of the company’s main strengths is its technical expertise. This encompasses not just the manufactureand sale of medical laboratory diagnostics, but also the diagnostic application of the products in a referencelaboratory which provides highly differential diagnostics. This reference laboratory has set standardsin Germany, and worldwide is unequalled in the whole field of autoimmune diagnostics. The diagnosticspectrum of the laboratory also covers the areas of infectious serology and serological allergy diagnostics.The reference laboratory receives hundreds of serum samples daily from all over Germany as well as frommany other countries. It helps EUROIMMUN customers to secure their results: a large proportion of serumsamples sent to EUROIMMUN for evaluation are analysed free of charge in order to maintain highstandards in the laboratories of EUROIMMUN customers. Customers can obtain further technicalinformation from experienced scientists in the company, with whom they can also discuss serologicalproblem cases. The “Institute for Quality Assurance”, an institution newly founded by EUROIMMUN,organises unbiased quality assessments and provides advice in the area of quality management. MoreoverEUROIMMUN has established the “Institute for experimental Immunology”, which is engaged in basicresearch.

In October 2009, the EUROIMMUN workforce included 134 university and college graduates, amongthese biologists, biochemists, chemists, engineers and medical doctors (40 of them holding a doctor’s degree).Medical technicians are particularly strongly represented with 116 people, corresponding to EUROIMMUN’sactivities, as well as biology/chemistry laboratory technicians (55). At present the company is training 51 youngpeople as biology laboratory assistants, industrial clerks, IT specialists, electronic system technicians, electronictechnicians for devices and systems, industrial mechanics, lathe operators and cooks as well as businessinformation technology specialists and business economists (dual system). At EUROIMMUN great value isplaced on advising customers and prospective customers in a factual, technical and commerciallyrestrained manner and fully supporting them in the use of our diagnostically demanding products.EUROIMMUN products are backed by an energetic and competent sales force, qualified information material,didactic test instructions and scientifically based, but nevertheless understandable advertisements in technicaljournals. Advertising material is produced in-house using the latest desktop publishing methods, right up untilthe fully digitalised ready-for-exposure documents. The most important publications and posters are translatedinto many languages. EUROIMMUN has set up an informative homepage on the internet(www.euroimmun.com) which is visited extensively internationally.

Over 3,000 laboratories worldwide use EUROIMMUN diagnostics. 400 of these are in Germany. Thecompany’s development is shaped by continuous growth. Although the diagnostic market in Germanystagnated and has become particularly strongly competitive, EUROIMMUN has been able to continue its strongexpansion. The company is achieving an ever increasing independence from the German market, since moreand more products are sold abroad. With their quality and standardization, EUROIMMUN products arecapturing the leading position in the world.


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TECHNIQUES FOR THE SEROLOGICAL INVESTIGATION OF ANTIBODIES


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FITC

FITC

cell withantigen

specific humanantibody

FITC-labelled anti-human antibody

Principle of the Test

• For the determination of autoantibodies or antibodies against infectious agents,cells, tissue sections or purified, biochemically characterized substances areused as antigen substrates.

• If the sample is positive, specific antibodies in the diluted serum sample attachto the antigens coupled to a solid phase.

• In a second step, the attached antibodies are stained with fluorescein-labelledanti-human antibodies and visualized with the fluorescence microscope.

• Positive samples can be titrated in steps. The most suitable titration interval isprovided by the dilution factor 3.162 (square root of 10). In this way, everysecond step represents in its denominator an integral power of 10 (1 : 10, 1 : 32,1 : 100, 1 : 320, 1 : 1000, 1 : 3200, 1 : 10000 etc.).

Indirect Immunofluorescence: A Standardized Technique for theDetermination of Autoantibodies and Antibodies againstInfectious Agents

• High specificity: positive and negative samples produce a large difference insignal strength. Each bound antibody shows a typical fluorescence patterndepending on the location of the individual antigens.

• The entire antigen spectrum of the original subtrate is available, thus allowingthe detection of a large number of antibodies and achieving a higher detectionrate.

• Immunofluorescence enables simultaneous detection of antibodies againstseveral biochemically different antigens on one single biological substrate.

• The indirect immunofluorescence test is the analytical method of choice when itwould be too difficult or too complicated to prepare the test antigens indi-vidually for enzyme immunoassays.

Pattern homog. Anti-dsDNA? Anti-Histones?

EUROIMMUN’s Innovations for the Standardization and Modern-ization of Indirect Immunofluorescence

• Activation technique: physically or chemically activated cover glasses are coatedwith cultured cells or tissue sections. Frozen tissue sections are fixed to theglass surface by covalent bonding, increasing adhesion more than 100 timesand thus preventing the substrates from being detached.

• BIOCHIP Technology: cover glasses coated with biological substrates are cutinto millimetre-sized fragments (BIOCHIPs) on a machine. This makes it possibleto obtain ten or more first-class preparations of homogeneous quality per tissuesection, in the case of cultured cell substrates even several thousands.

• BIOCHIP Mosaics™: using several BIOCHIPs coated with different substrates sideby side on one and the same reaction field, antibodies against various organs orinfectious agents can be investigated simultaneously. Detailed antibody profilescan thus be established with comparatively little effort, allowing the reciprocaldetermination of the results on different substrates.

• TITERPLANE™ Technique: samples or reagents are applied to the reaction fieldsof a reagent tray. The BIOCHIP Slides are then placed into the recesses of thereagent tray, where all BIOCHIPs come into contact with the fluids, and theindividual reactions commence simultaneously. As the fluids are confined in aclosed space, there is no need for the use of a conventional „humidity chamber“.

Pattern fine-granular.Anti-SS-A? Anti-SS-B?

Pattern nucleolar. Anti-PM-Scl?

Pattern cytoplasmic.AMA M2?

Differentiation of antibodies using HEp-2 cells.

Indirect Immunofluorescence: An Easy and Modern Method

BIOCHIP Technology and Mosaics.

tissue sections

antigen dots

culture cells

transf. cells


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Chemically Activated Cover Glasses for Histochemistry

• For diagnostics of organ-specific or tissue-specific autoantibodies frozen tissuesections of various organs are used. However, formerly, the morphology oftissues suffered during incubation in aqueous medium, tissue parts occasionallybecame detached from slides, and the interpretation of results was difficult.

• Using the activation technique for the first time in histology, we have appliedsolid phase techniques. Firstly, the surface of cover glasses is coated withspontaneously reactive aldehyde groups. In a second step, the tissue sectionsare applied to the chemically activated cover glasses (Stöcker, W: EuropeanPatent No. 0 117 262; U.S. Patent No. 4,647,543). Free amino groups of the tissuesections, especially of the hydroxylysine contained in the collagen, bind to thecarrier material by covalent bonding.

• This results in an increased adhesion of frozen tissue sections more than ahundredfold and prevents them from being detached during incubation.Furthermore, in some cases the activation technique results in a significantlybetter conservation of tissue structures, especially in organs which previouslyexhibited a generally low level of adhesion. Therefore, the tests can be evaluatedwith considerably greater confidence.

Fixation of frozen tissue sections to glasssurfaces by covalent bonding.

Determination of Low-Avidity Antibodies

• An alternative principle for the serological diagnosis of fresh infections has beenestablished by investigating the antibody avidity.

• The first reaction of the immune system following an infection is the formationof low-avidity antibodies. As the infection proceeds, increasingly antigen-adaptedIgG is formed, and avidity grows. As long as high-avidity IgG is not yet detectedin the serum, it can be assumed that the infection is still in an early stage.

• To identify low-avidity antibodies in a patient’s serum, two immunofluorescencetests are performed in parallel: one test is carried out in the conventional way,the other one includes urea treatment between incubations with patient’s serumand peroxidase-labelled anti-human IgG, resulting in the detachment of low-avidity antibodies from the antigens.

• Low-avidity antibodies are present if the fluorescence intensity is significantlyreduced (two intensity levels ore more) by urea treatment.

• The following test kits for avidity determination are available: Toxoplasmagondii, Rubella virus, West-Nile virus, CMV, EBV-EA, EBV-CA.

high-avide Ab against EBV-CA

low-avide Ab against EBV-CA

without urea with urea

Si

(CH2)3

NH

(CH2)2

N

(CH2)3

HC

HC

N

frozen tissue section

O

OSi

(CH2)3

NH

(CH2)2

N

(CH2)3

HC

HC O

NH2

frozen tissue section

O

OSi

(CH2)3

NH

(CH2)2

NH2

(CH2)3

HC O

HC O

glutardialdehyde

O

O

Si

(CH2)3

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NH2

OCH3

OCH3

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Aminoethyl-

aminoproyl-

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- H2O- 3 CH3OH - H2O

EUROPLUS™ System: Combination of conventional immuno-fluorescence substrates and monospecific tests

• In EUROPLUS™ immunofluorescence tests antibody detection is performedusing both tissue sections/cell substrates and monospecifically reactingantigens.

• Antibodies detected in IFT screening tests can therefore be differentiated orconfirmed with one and the same reaction field. In some cases, the antigenshelp to extend the antigen spectrum, offering a wider range for screening.

• BIOCHIPs coated with purified or recombinant antigens are used asmonospecific substrates.

• In case of a positive result the antigens fluoresce green in defined areas underthe microscope.

• In some EUROPLUS™ test systems several different antigens are coated on oneBIOCHIP in separate antigen rows. In this manner, several monospecific analysescan be performed using a single BIOCHIP.

• Available EUROPLUS™ substrates: MPO, PR3, gliadin GAF-3X, OspC, VlsE,Plasmodium falciparum und vivax, gp125, p19.

EUROPLUS™: BIOCHIP combination of tissuesections / cell substrates (left) and purifiedantigens (right).


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New: Hydrophobic Slides

• EUROIMMUN has developed a specific slide surface with hydrophobicproperties.

• This prevents the droplets from spreading on the slide surface. The slides arenow suitable for manual incubation using TITERPLANE Technique and non-manual incubation on automated systems.

• The reaction fields must not be marked with a Cytomation Pen anymore.

• Price and order number are the same as for conventional EUROIMMUN slides(please add "hydrophobic" when ordering)

• Hydrophobic slides are available on request for many products.

AP16 IF Plus by DAS: Automated Solution for all EUROIMMUNImmunofluorescence Tests

• Various validated parameters. Slide definitions and test files available.

• CE conformity for device/test system combination.

• Capacity: 16 slides, 80 samples, 200 dilutions.

• Programmable for 8 methods per run.

• 12 dilution series freely programmable.

• Automated sample dilution, sample and reagent dispension, incubation andwashing of slides.

• Laboratory software interface.

• The incubation protocol for result documentation is automatically created fromthe worklist.

• Barcode reader available on request.

Fluorescence Microscope EUROStar II

• The EUROStar II is specifically tailored to the requirements of indirect immuno-fluorescence. Unnecessary and partly expensive components have been de-liberately left out of the design and the conventional complex illuminationfittings have been replaced by the stunningly simple EUROStar Bluelight system.

• With the EUROStar Bluelight, engineers at EUROIMMUN AG have introducedblue light-emitting diodes to fluorescence microscopy. Almost all the emittedlight is suitable for the excitation of fluorescein.

• The EUROStar Bluelight does not emit any ultraviolet radiation and is explosionproof.

• The EUROStar Bluelight is immediately ready for operation after being switchedoff and offers instant full output after being switched on again. The LED shinesfor 50,000 hours – which is 500 times longer than a mercury vapour lamp. Thus,the microscope requires almost no maintenance.

• With its halogen transmitted-light source, the version EUROStar II Plus is suitedfor brightfield, darkfield, phase contrast or polarisation microscopy.

• EUROStar was designed to accommodate the additional assembly of a digitalcamera.

Above: conventional slideBelow: hydrophobic slide.

AP16 IF Plus by DAS.


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BIOCHIP Mosaics™

Slides for indirect immunofluorescence can be produced with single substrates or BIOCHIP Mosaics™from up to 45 different substrates according to your individual requirements. thyroid gland, parathyroidgland, pancreas, adrenal gland, ovary, placenta*, testis, spermatozoa, pituitary gland, hypothalamus*, cerebrum,cerebellum, brain stem, pons*, lobus temporalis, substantia nigra*, peripheral nerve, spinal cord, optic nerve (AQP-4,NMO IgG) eye, granulocytes (fixed with EOH, HCHO or MOH), lactoferrin-specific granulocytes, lymphocytes,monocytes*, thrombocytes, kidney (primate, rat, mouse), lung*, liver (primate, rat, mouse), mouth mucosa, stomach(corpus, antrum), jejunum, colon, intestinal goblet cells, umbilical cord, mamma, lacrimal gland, parotid gland,prostate, vesicula seminalis, skeletal muscle, F-actin (VSM47), heart muscle, thymus, lipocytes, cartilage*, epidermis,oesophagus (primate, rat), tongue, lip, melanocytes, HEp-2 cells, HEp-20-10 cells, HUVEC, Crithidia luciliae sensitiveetc. Adenovirus, Afipia felis*, Bartonella henselae, B. quintana, Bordetella parapertussis, B. pertussis, Borrelia afzelii,B. burgdorferi sensu stricto (strains CH, USA), B. garinii, Campylobacter coli*, C. jejuni, Candida albicans, C. glabrata*,C. krusei*, C. parapsilosis*, C. tropicalis*, Chikungunya virus, Chlamydia pneumoniae, C. trachomatis, C. psittaci, CMV,Coxsackievirus (A7, A9, A16, A24, B1 to B6), Crimean Congo fever virus, Dengue virus type 1 to 4, EBV-CA, EBNA, EBV-EA, Echinococcus granulosus, ECHO virus, Hantavirus, Haemophilus influenzae*, Helicobacter pylori, HHV-6, HSV-1,HSV-2, Influenza virus A (strains H3N2, H1N1, H5N1), Influenza virus B, Japanese encephalitis virus, Klebsiellapneumoniae*, Legionella bozemanii*, L. dumoffii*, L. gormanii*, L. jordanis*, L. longbeachae, L. micdadei*,L. pneumophila (serotypes 1 to 14), Leishmania donovani, Listeria monocytogenes (1/2a and 4b)*, measles virus,mumps virus, Mycoplasma hominis, M. pneumoniae, Parainfluenza virus type 1 to 4, Rift valley fever virus*, RSV,rubella virus, Saccharomyces cerevisiae, SARS-CoV, TBE virus, TO.R.C.H. profile, Toxoplasma gondii, Treponemapallidum, T. phagedaenis, Ureaplasma urealyticum, VZV, West Nile virus, Yellow fever virus, Yersinia enterocolitica(O:3, O:4, O:6 and O:9)*. EUROPLUS™: HEp-2/liver + RNP/Sm, Sm, SS-A, SS-B, Scl-70, rib. P-proteins, Jo-1;granulocytes + MPO, PR3; primate stomach (parietal cells) + intrinsic factor; primate liver (endomysium) + gliadin(GAF-3X); rat kidney + AMA M2; thyroid gland + thyroglobulin; Borrelia burgdorferi and afzelii + OspC and VlsE,Plasmodium falciparum (HRP-2, MSP-2), P. vivax (MSP, CSP). Transfected cells: rPAg 1 + 2 (pancreas antigen 1 + 2),AQP-4, glutamate receptor (type NMDA), desmoglein 1 + 3, BP230. * Currently not available in the European Union.


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(Reaction fields 5 x 5 mm)

The TITERPLANE™ Technique was developed by EUROIMMUN in order to standardize immunologicalanalyses: Samples or labelled antibodies are applied to the reaction fields of a reagent tray. The BIOCHIPSlides are then placed into the recesses of the reagent tray, where all BIOCHIPs of the slide come into contactwith the fluids, and the individual reactions commence simultaneously. Position and height of the droplets areexactly defined by the geometry of the system. As the fluids are confined in a closed space, there is no need forthe use of a conventional ”humidity chamber”. It is possible to incubate any number of samples next to eachother and simultaneously under identical conditions.

Prepare: Check the reagent tray: Are the reaction fields hydrophiIic and the surrounding coating hydrophobic?If not, rub with a wet paper towel, using normal household detergent or Extran MA 01 (Merck) if necessary, andrinse thoroughly with water. For occasional disinfection, immerse for 1 h in 3% Sekusept Extra (Henkel) inwater. Open the individual packets containing the BIOCHIP Slides only after they have reached roomtemperature. Do not touch the BIOCHIPs. Mark BIOCHIP Slides as required with a felt pen.

Dilute: Dilute serum samples according to the user’s test protocol. Include positive and negative controls withevery test procedure. Mix control sera before use.

Pipette: Apply 25 µl of diluted serum to each reaction field of the reagent tray, avoiding air bubbles. Transferall samples to be tested before starting the incubation (up to 200 droplets). Use a polystyrene pipettingtemplate.

Incubate: Start reactions by fitting the BIOCHIP Slides into the corresponding recesses of the reagent tray.Ensure that each sample makes contact with its BIOCHIP and that the individual samples do not come intocontact with each other. Incubate for 30 min at room temperature.

Wash: Rinse the BIOCHIP Slides with a flush of PBS-Tween using a beaker, and immerse them immediatelyafterwards in a cuvette containing PBS-Tween for at least 5 min.

Pipette: Apply 20 µl of fluorescein-labelled anti–human immunoglobulin (conjugate) onto each reaction fieldof a clean reagent tray. Add all drops (reagent for a maximum of 50 slides) before continuing incubation. Use astepper pipette. The labelled anti-human serum should be mixed with a pipette before use. To save time,conjugate can be pipetted onto separate reagent trays during incubation with the diluted serum.

Incubate: Remove one BIOCHIP Slide from the PBS-Tween and within five seconds blot only the back and thelong edges with a paper towel and immediately put the BIOCHIP Slide into the recesses of the reagent tray. Donot dry the areas between the reaction fields. Check for correct contact between the BIOCHIPs and liquids.Then continue with the next BIOCHIP Slide. From now on, protect the slides from direct sunlight. Incubate for30 min at room temperature.

Wash: Rinse the BIOCHIP Slides with a flush of PBS-Tween using a beaker and put them in a cuvette containingPBS-Tween for at least 5 min. 10 drops of Evans Blue (150 µl) for each 150 ml phosphate buffer can be addedfor counterstaining.

Embed: Place glycerol/PBS onto a cover glass – drops of 10 µl per reaction field. Use a polystyrene embeddingtemplate. Remove one BIOCHIP Slide from the PBS-Tween and dry the back and all four edges as well as thesurface around, but not between, the reaction fields with a paper towel. Put the BIOCHIP Slide, with theBIOCHIPs facing downwards, onto the prepared cover glass. Check immediately that the cover glass is properlyfitted into the recesses of the slide. Correct the position if necessary. Now proceed in the same way with the nextBIOCHIP Slide.

Evaluate: Read the fluorescence under the microscope.

The Indirect Immunofluorescence Test, Performed Using the

TITERPLANE™ Technique


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The Indirect Immunofluorescence Test, Performed Using the

TITERPLANE™ Technique

Pipette:10 µl per field (3 x 3 mm)25 µl per field (5 x 5 mm)70 µl per field (7 x 9 mm)

Pipette:10 µl per field (3 x 3 mm)20 µl per field (5 x 5 mm)60 µl per field (7 x 9 mm)

Embed:10 µl per field (3 x 3 mm)10 µl per field (5 x 5 mm)20 µl per field (7 x 9 mm)

Incubate: 30 min

Incubate: 30 min

Evaluate: fluorescence microscopy

Wash: 1 s flush5 min cuvette


slide

reagent trayBIOCHIPs

diluted samples

PBS-Tween

labelled antibody

PBS-Tween

glycerol/PBS

cover glass


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Recommended Serum Dilutions for Indirect Immunofluorescence

– Autoimmunity –

Antibodies against Substrate IgA IgG IgM IgAGM

*) In addition to the preferential analysis or as a plausibility check.**) Hepatitis Mosaic: liver, monkey / heart, monkey / HEp-2 cells / liver, rat / kidney, rat / stomach, rat.

acetylcholine receptor *skeletal muscle, monkey / heart, monkey 100actin Hepatitis Mosaic** 10 10 100ADH-producing cells nucl. supraopticus & paraventricularis, monkey 10 10adrenal cortex adrenal gland, monkey 10alveolar basement membrane lung, monkey / kidney, monkey 10

aquaporin-4 Neurology Mosaic 10asialoglycoprotein receptors *Hepatitis Mosaic** 100basic myelin protein (BMP) cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100bile canaliculi Hepatitis Mosaic** 100 100bile duct epithelium Hepatitis Mosaic** 10 + 100

BP180 Dermatology Mosaic (EUROPLUS) 10BP230 Dermatology Mosaic (transfected cells) 10brain: grey matter cerebellum, monkey / intestinal tissue, fetal monkey 10 + 100 10brain: white matter cerebellum, monkey / intestinal tissue, fetal monkey 10 + 100 10cANCA granulocytes (EOH), human / liver, monkey 10 10 + 100 1

cartilage trachea, fetal monkey 10 10cell nuclei (ANA) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100CENP-F *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100centromere HEp-2 cells / liver, monkey 100 + 1000 + 10000 100cerebrum gyrus precentralis, monkey 10 + 100 10

chondroitin sulfate trachea / cartilage, monkey 10 10 10collagen type VII oesophagus, monkey or tongue, monkey 10 10collagenous connective tissue pancreas, monkey 10 10colon (epithelial cells) intestinal tissue, fetal monkey 10 10cornea eye, monkey 10 10

cyclin I (PCNA) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100cyclin II (mitosin) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100cytoskeleton HEp-2 cells / liver, monkey 100 100 + 1000 + 10000 100desmoglein 1+3 transfected cells 10desmosomes oesophagus, monkey or tongue, monkey 10

dsDNA *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100dsDNA Crithidia luciliae 10 10elastin stomach, rat / kidney, rat 10endocardium endocardium, monkey / intestinal tissue, fetal monkey 10endomysium liver, monkey 10 10

endoplasmatic reticulum HEp-2 cells / liver, monkey 100 + 1000 + 10000 100endothelial cells lung, monkey 10 10endplates *skeletal muscle, monkey / heart, monkey 100enterocytes intestinal tissue, fetal monkey 10 10eosinophilic granulocytes granulocytes (EOH) / liver, monkey 10 10 + 100 1

epidermal basement membrane oesophagus, monkey or tongue, monkey 10 10eye muscle eye, monkey 10fibrillarin (U3-nRNP) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100filaggrin oesophagus, rat 10 10ganglion cells ganglion stellatum, monkey / intestinal tissue, fetal monkey 10 10

gastric mucosa stomach, monkey 10gastrin-producing cells stomach (antrum), monkey / stomach (corpus), monkey 10 10glandula suprarenalis adrenal gland, monkey 10gliadin *intestinal tissue, fetal monkey / gliadin dots 10 10glomerular basement membrane (GBM) kidney, monkey 10 10

glutamate receptor type NMDA transfected cells 10glutamic acid decarboxylase (GAD) cerebellum, monkey / pancreas, monkey 10 + 100 10goblet cells goblet cells (culture) 10 10Golgi apparatus HEp-2 cells / liver, monkey 100 + 1000 + 10000 100hair follicle epidermis, monkey 10 10


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heart muscle skeletal muscle, monkey / heart, monkey 100 100heart valves mitral valve, monkey 10 10histones *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100Hu cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100hypothalamus nucl. supraopticus & paraventricularis, monkey 10 10inner ear inner ear, rat or guinea pig 10 10intercalated discs heart, monkey 100 100intestinal epithelial tissue intestinal tissue, fetal monkey 10 10intrinsic factor *stomach, monkey / intrinsic factor 10 10Jo-1 *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

keratin oesophagus, monkey or tongue, monkey 10 10keratin, RA-associated (filaggrin) oesophagus, rat 10 10Ku *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100labyrinth inner ear, rat or guinea pig 10 10lacrimal gland (excretory ducts and acini) lacrimal gland, monkey 10 10

laminin epidermis, monkey / lung, monkey / kidney, monkey 10 10lamins HEp-2 cells / liver, monkey 100 + 1000 + 10000 100lipocytes fat tissue, monkey 10 10liver membrane (LMA) Hepatitis Mosaic** 100liver-kidney microsomes (LKM) Hepatitis Mosaic** 100

liver-pancreas antigen (LP) Hepatitis Mosaic** / pancreas, monkey 100liver-specific protein (LSP) Hepatitis Mosaic** 100lymphocytes Lymphocytes 10 + 100 10 + 100lysosomes HEp-2 cells / liver, monkey 100 + 1000 + 10000 100M2 *Hepatitis Mosaic** 100 + 1000 + 10000 100

M3 *Hepatitis Mosaic** 100 + 1000 + 10000 100M4 *Hepatitis Mosaic** 100 + 1000 + 10000 100M5 *Hepatitis Mosaic** 100 + 1000 + 10000 100M6 *Hepatitis Mosaic** 100 + 1000 + 10000 100M7 *Hepatitis Mosaic** 100 + 1000 + 10000 100

M8 *Hepatitis Mosaic** 100 + 1000 + 10000 100M9 *Hepatitis Mosaic** 100 + 1000 + 10000 100medullated nerves cerebellum, monkey / nerves, monkey 10 + 100melanocytes retina, monkey 10 10Mi-1 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

Mi-2 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100mitochondria (AMA) kidney, rat / stomach, rat / M2 dots / HEp-2 cells 100 + 1000 + 10000 100mouth mucosa mouth mucosa 10 10 10myelin cerebellum, monkey / nerves, monkey 10 + 100myelin-associated glycoprotein (MAG) cerebellum, monkey / nerves, monkey 10 + 100

myeloperoxidase (MPO) granulocytes (EOH), human / liver, monkey 10 10 + 100 1myocardium skeletal muscle, monkey / heart, monkey 100 100myolemma skeletal muscle, monkey / heart, monkey 10 + 100 10 + 100myosin skeletal muscle, monkey / heart, monkey 100 100native collagen pancreas, monkey 10

nerves cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100neuroendothelium cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100neurofilaments cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100NOR HEp-2 cells / liver, monkey 100 + 1000 + 10000 100nRNP HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

ovary ovary, monkey 10 10pANCA granulocytes (EOH), human / liver, monkey 10 10 + 100 1pancreas acini (Crohn’s disease autoantigen) pancreas, monkey 10 10pancreas islets pancreas, monkey (1st step: 18 hours) 10 10pancreas, excretory duct epithelium pancreas, monkey 10 10 10




*) In addition to the preferential analysis or as a plausibility check.**) Hepatitis Mosaic: liver, monkey / heart, monkey / HEp-2 cells / liver, rat / kidney, rat / stomach, rat.


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parathyroid gland parathyroid gland, monkey 10 10parietal cells stomach (corpus), monkey 10 10 10 + 100parotid gland parotid gland, monkey 10 10peripheral nerves cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100pituitary gland, anterior lobe pituitary gland, monkey 10 10placenta placenta, human 10PM-1 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100proinsulin *pancreas, monkey 10 10prostate prostate, monkey 10proteinase 3 (PR3) granulocytes (EOH), human / liver, monkey 10 10 + 100 1

Purkinje cell cytoplasm (Yo) cerebellum, monkey 10 + 100 10 + 100RANA Raji cells / HEp-2 cells 10 10reticulin intestinal tissue, fetal monkey 10 10 10reticulocytes bone marrow, monkey 10 10retina retina, monkey 10 10

Ri cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100ribosomal P-proteins HEp-2 cells / liver, monkey 100 + 1000 + 10000 100ribosomes HEp-2 cells / liver, monkey 100 + 1000 + 10000 100RNA polymerase HEp-2 cells / liver, monkey 100 + 1000 + 10000 100RNA HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

salivary glands (acini and excretory ducts) parotid gland, monkey 10 10sarcolemma skeletal muscle, monkey / heart, monkey 10 + 100 10 + 100Scl-70 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100signal recognition particle (SRP) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100skeletal muscle skeletal muscle, monkey / heart, monkey 100 100

Sm HEp-2 cells / liver, monkey 100 + 1000 + 10000 100smooth muscles (ASMA) stomach, rat / kidney, rat 100 100spermatozoa spermatozoa smear, human 10 10 10spindle fibers HEp-2 cells / liver, monkey 100 + 1000 + 10000 100spleen spleen, monkey 10 + 100

SS-A (Ro) *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100SS-B (La) *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100ssDNA *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100striated muscles skeletal muscle, monkey / heart, monkey 100 100substantia nigra substantia nigra, monkey 10 10 + 100

synovialis joint cartilage, monkey 10 10testis testis, monkey 10 10thrombocytes (bound antibodies) thrombocyte smear – – –thrombocytes (free antibodies) thrombocytes, human 10 10 10thymus thymus, monkey 10 10

thyroglobulin thyroid gland, monkey or struma, human/TG 10 + 100 10thyroid colloid type II thyroid gland, monkey or struma, human 10 10thyroid microsomes thyroid gland, monkey or struma, human 10 + 100 10trachea trachea, monkey 10 10tubular basement membrane kidney, monkey 10 10

U1-nRNP *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100vasopressin-producing cells nucl. supraopticus & paraventricularis, monkey 10 10vestibular organ inner ear, rat or guinea pig 10 10vimentin *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100”xANCA” granulocytes (EOH, acetone, HCHO) / liver, monkey 10 10 + 100 1




*) In addition to the preferential analysis or as a plausibility check.


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Antibodies against IgA IgG IgM


– Infectious Serology –

Adenovirus (type 3) 10 + 100 10 + 100 10Afipia felis 100 100 + 1000 10Bartonella henselae 100 + 320 + 1000 100Bartonella quintana 100 + 320 + 1000 100Bordetella parapertussis 10 + 100 100 + 1000 100 + 1000

Bordetella pertussis 10 + 100 100 + 1000 100 + 1000Borrelia afzelii 100 + 320 + 1000 10Borrelia burgdorferi sensu stricto (strains CH and USA) 100 + 320 + 1000 10Borrelia garinii 100 + 320 + 1000 10Borrelia OspC 10

Borrelia VlsE 100Campylobacter coli 100 100 + 1000 10Campylobacter jejuni 320 1000 100Candida albicans 100 + 1000 1000 + 10000 100Candida glabrata 100 + 1000 1000 + 10000 100

Candida krusei 100 + 1000 1000 + 10000 100Candida parapsilosis 100 + 1000 1000 + 10000 100Candida tropicalis 100 + 1000 1000 + 10000 100Chikungunya virus 10 + 100 10 + 100Chlamydia pneumoniae (IFA) 100 100 + 1000 10

Chlamydia pneumoniae (MIF) 10 100 10Chlamydia trachomatis (IFA) 100 100 + 320 + 1000 10Chlamydia trachomatis (MIF) 10 100 10Chlamydia psittaci (MIF) 10 100 10CMV 100 100 + 1000 100

Coxsackie virus types A7, A9, A16, A24, B1 to B6 10 + 100 100 + 1000 10Dengue virus 10 100 + 1000 10 + 100EBV-CA, -EA 10 + 100 10 + 100 + 1000 10 + 100EBNA 10 + 100Echinococcus granulosus 100 100 + 320 + 1000 100

Echo virus (type 7, 19) 10 + 100 100 + 1000 10Hanta virus 100 + 1000 100 + 1000 100 + 1000Haemophilus influenzae 100 1000 + 10000 10Helicobacter pylori 100 100 + 1000 10HIV-1/2 10 + 100

HHV-6 10 + 100 10HSV-1/2 10 100 + 1000 + 10000 10Influenza virus type A 10 10 + 100 10Influenza virus type B 10 10 + 100 10Klebsiella pneumoniae 100 100 100

Legionella pneumophila (all serotypes) 100 + 320 + 1000Leishmania 100 320 100Listeria monocytogenes (type 1/2a, 4b) 100 100 + 1000 100measles virus 10 10 + 100 10mumps virus 10 10 + 100 10

Mycoplasma hominis 10 10 + 100 10Mycoplasma pneumoniae 10 10 + 100 10Parainfluenza virus types 1 - 4 10 + 100 10 + 100 + 1000 10Plasmodium falciparum/vivax 32 + 100

rubella virus 10 + 100 10 + 100 10 + 100RSV 10 10 + 100 + 1000 10Saccharomyces cerevisiae 100 1000 100TBE virus 10 10 + 100 + 1000 10 + 100Toxoplasma gondii 16+64+256 16+64+256+1028... 16+64+256

Treponema pallidum 10 10 + 100 10Ureaplasma urealyticum 10 10 + 100 10VZV 10 10 + 100 10West-Nile virus 10 + 100 + 1000 10 + 100Yersinia enterocolitica O:3; O:4; O:6; O:9 10 + 100 100 10 + 100


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Diagnostically Relevant Autoantibodies

Systemic Autoantibodies against

Grey boxes: standard analysis *) ANCA diagnostics in acute cases within one hour, at any hour **) Use special procedure for taking sample(s) ***) Send frozen sample(s)

Ig- AGM A G M SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)151 ANA (cell nuclei) IF global testing1574 nucleosomes SLE specific1572 dsDNA ELISA1572 dsDNA IFT (C. luciliae) SLE specific1572 dsDNA RIA159 ENA PoolPlus ELISA1591 U1-nRNP1593 Sm SLE specific1595 SS-A (Ro)159s SS-A 52 kDa: recombinant159t SS-A 60 kDa: recombinant1597 SS-B (La)1640 ribosomal P proteins SLE specific1605 Ku1601 cyclin I (PCNA)156 histones (global testing)1576 ssDNA (single-stranded DNA)121 pANCA* (granulocytes) vasculitis

CIRC. IMMUNE COMPLEXES1818 C1q ELISA

Ig- AGM A G M BASIS SPECTRUM151 ANA (cell nuclei) IF global testing152 ANA profile differentiation1572 dsDNA-NcX ELISA1572 dsDNA IFT SLE specific1590 ENA ProfilePlus ELISA 1 nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-11590 ENA ProfilePlus ELISA 2 rib. P proteins, RNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, CENP B1590 SLE Profile ELISA (dsDNA, histones, rib. P prot., nRNP/Sm, Sm, SS-A, SS-B, Scl-70)162 AMA (mitochondria)171 ASMA (smooth muscle)120 cANCA* (granulocytes) Wegener’s dis.121 pANCA* (granulocytes) vasculitis1010 autoantibody profile 10 IF substrates1030 autoantibody profile 30 IF substrates

Ig- AGM A G M POLYMYOSITIS, DERMATOMYOSITIS151 ANA (cell nuclei) IF global testing1530 Myositis Profile 3 EUROLINE (Mi-2, Ku, PM-Scl100, PM-Scl75, SRP, Jo-1, PL-7, PL-12, OJ, EJ, Ro-52)1661 Jo-11662 PL-71663 PL-121664 OJ1665 EJ1666 SC1667 KS1584 PM-Scl (PM-1)1616 SRP (signal recognition particle)159s SS-A 52 kDa: recombinant1605 Ku1607 Mi-21635 serotonin ab1636 PMR (polymyalgia rheumatica factor)

Ig- AGM A G M OTHER AUTOANTIBODIES1612 centrioles1613 MSA-1 (NuMa, spindle fibres)1614 MSA-2 (midbody)1615 MSA-3 (chromosome-ass. antigen)1617 centromer F protein (CENP-F)1641 ribosomes1642 Golgi apparatus1643 lysosomes165 cytoskeleton1651 actin1652 vimentin1653 cytokeratin1654 tropomyosin1655 vinculin1656 desmin1659 laminin (basal membranes)194 collagen (global testing)1947 collagen type VII1950 elastin196 vessel endothelium

Ig- AGM A G M PROGRESSIVE SYSTEMIC SCLEROSIS151 ANA (cell nuclei) IF global testing1599 Scl-70 (DNA topoisomerase I)1584 PM-Scl (PM-1)1611 centromeres1611 centromere B protein (recombinant)1582 U3-nRNP (fibrillarin)1583 RNA polymerase I, II, III1585 7-2-RNP (To)1586 4-6-S-RNA1587 NOR (nucleolus organizer region)

Ig- AGM A G M (RHEUMATOID) ARTHRITIS1505 CCP (cyclic citrullinated peptides)151a Sa1814 RF IgM (class. rheumatoid factor)1508 filaggrin (RA keratin)1219 GS ANA (granulocyte specific ANA)151 ANA (cell nuclei) IF global testing1604 RANA (rheum. arthritis nuclear antigen)121 pANCA* (granuloc.) RF-ass. vasculitis148 cartilaginous subst. polychondritis194 collagen (global testing)1947 collagen type VII

Ig- AGM A G M THERAPY CONTROL1821 interferon alpha***1822 interferon beta1824 erythropoetin1572 dsDNA RIA1818 CIC-C1q ELISA

Ig- AGM A G M ANA DIAGNOSTICS, WESTERNBLOT1520 PM-Scl, CENP A/B, Ku 86 and 72 kDa, M2 74 kDa, RNP 70 kDa, RNP A/C, Sm B/B’/D, SS-A 60 and 52 kDa, SS-B 52, 47, 44 and 43 kDa, ribosomal P proteins P0/P1/P2, Scl-70, Jo-1)

FURTHER RHEUMATOID RELEVANT Ig- AGM A G M ANALYSES2011 anti-streptolysin2012 anti-streptokinase2013 anti-streptodornase2014 anti-DPNase (anti-NADase)2031 anti-staphylolysin2034 anti-hyaluronidase213 Borrelia burgdorferi2171 Yersinia enterocolitica O:32191 Chlamydia trachomatis

IMMUNOGLOBULINS: Ig- AGM A G M ANTI-1811 human IgA1813 human IgE1814 human IgG1815 human IgM

Ig- AGM A G M SJÖGREN’S SYNDROME151 ANA (cell nuclei) IF global testing1595 SS-A (Ro)159s SS-A 52 kDa: recombinant159t SS-A 60 kDa: recombinant1597 SS-B (La)

Ig- AGM A G M ANTI-PHOSPHOLIPID SYNDROME (APS)1621 cardiolipin1632 ß-2-glycoprotein 11631 lupus anticoagulant (plasma)**162a phosphatidylserine

Ig- AGM A G M SHARP’S SYNDROME MCTD1591 U1-nRNP151 ANA (cell nuclei) IF global testing

Ig- AGM A G M CREST SYNDROME1611 centromeres1611 centromere B protein (recombinant)


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Diagnostically Relevant Autoantibodies

Grey: standard *) ANCA diagn. in acute cases within 1 h **) Special procedure for taking sample ***) CV2 partial protein, which only contains the N-terminally localised epitopes of the antigen

Organ-/Tissue-Specifi c Autoimmunity: Autoantibodies against

Ig- AGM A G M AUTOANTIBODY PROFILE1030 30 IF substrates (BIOCHIPs)

Ig- AGM A G M THYROID GLAND1015 TRAb (TSH receptors)1012 TPO ab (thyroidea peroxidase)1013 TAb (thyroglobulin)1014 colloid antigen II ab1011 MAb (microsomes)1016 T3 ab1017 T4 ab

Ig- AGM A G M DIABETES MELLITUS1021 ICA (islet cell antibodies)1022 GAD (glutamic acid decarboxylase)1023 IA-2 (tyrosine phosphatase)1024 insulin ab human1025 insulin receptor1026 glucagon-producing cells147 lipocytes

Ig- AGM A G M (POLY-)ENDOCRINOPATHY1051 adrenal cortex Addison’s dis.1053 21-hydroxylase Addison’s dis.1061 ovary: theca cells1062 ovary: corpus luteum1081 testis: Leydig cells105 steroid hormon-producing cells104 parathyroid gland1021 ICA (islet cell antibodies)1012 TPO ab (thyroidea peroxidase)1361 H+/K+-ATPase ab ELISA1361 PCA (parietal cells)1091 pituitary gland: anterior lobe1092 pituitary gland: posterior lobe1011 MAb (thyroid microsomes)1052 adrenal medulla107 placenta110 VPZ (vasopr.-prod. cells) D. insipudus

Ig- AGM A G M INFERTILITY1621 cardiolipin1060 ovary: theca c., c. luteum, z. pellucida1081 testis: Leydig cells1086 spermatozoa1091 pituitary gland: anterior lobe107 placenta1401 prostate

Ig- AGM A G M NERVOUS SYSTEM111 Neuronal Ab IFT global testing

Paraneoplastic neurol. syndromes1111 Neuronal Antigens Profile 2 EUROLINE amphiphysin, CV2.1***, PNMA2 (Ma-2), Ri, Yo, Hu1112 Tr (Purkinje cell cytoplasm)1113 Yo (Purkinje cell cytoplasm; PCA-1)1114 PCA-2 (Purkinje cell cytoplasm)1115 Ri (neurone nuclei; ANNA-2)1116 Hu (neurone nuclei; ANNA-1)112d NMDA receptors1117 Ma1/Ma2 (neurone nuclei; Ta)1119 CV2 (oligodendrocytes)1022 GAD stiff-person syndr.112e amphiphysin stiff-person syndr.112a AGNA (anti-glia nuclear antigen; SOX-1)112b ANNA-3112c CRMP-5 (oligodendrocytes)

further parameters1154 aquaporin-4 neuromyelitis optica1153 NMO-IgG neuromyelitis optica1156 MOG (myelin-oligodendroc. glykoprot.)1111 substantia nigra1121 myelin1122 MBP (myelin-basic protein)1123 MAG (myelin-assoc. glycoprotein)1124 myelin of peripheral nerves1126 neuroendothelium1127 neurofilaments1128 GFAP (glial fibrillary acidic protein)1129 non-medullated nerves112f astrocytes112g basal ganglia112h ganglion stellatum112i plexus myentericus112j synaptophysin1130 ganglioside profile GM1, GM2, GM3, GD1a, GD1b, GT1b, GQ1b1131 GM11132 GM21133 GM31134 GD1a1135 GD1b1136 GT1b1137 GQ1b1155 neurofascin151 ANA (cell nuclei) IF global testing213 Borrelia burgd.: serum CSF

Ig- AGM A G M WEGENER’S DISEASE, VASKULITIS*120 cANCA IFT* granuloc. Wegener’s dis.1201 PR3 (proteinase 3)1202 BPI (CAP 57)121 pANCA IFT* granulocytes vasculitis1211 MPO (myeloperoxidase)1212 elastase1213 cathepsin G1215 lactoferrin120 ANCA Profile ELISA PR3, MPO, elastase, cath. G, BPI, lactoferrin151 ANA (cell nuclei) IF global testing195 elastin196 vessel endothelium

Ig- AGM A G M EYE1178 recoverin1177 tunica choroidea chron. chorioretinitis1171 cornea1172 retina1173 lens oculi1174 corpus ciliare1175 eye muscles1176 retro bulbar connective tissue other:1119 CV2 (oligodendrocytes)120 cANCA* (granulocytes) Wegener’s dis.151 ANA (cell nuclei) IF global testing

Ig- AGM A G M IMMUNOHAEMATOLOGY124 erythrocytes (global testing)1209 granulocyte membrane1221 lymphocytes1231 thrombocytes: indirect test (free ab)1232 thrombocytes: direct test (bound ab)**1361 H+/K+-ATPase ab ELISA1361 PCA (parietal cells)

Ig- AGM A G M SKELETAL MUSCLE, THYMUS1435 acetylcholine receptors M. gravis1434 MuSK M. gravis1437 calcium channels type N LEMS1438 calcium channels type PQ LEMS1439 potassium channel ab (VGKC)144 thymus M. gravis, thymoma1431 titin M. gravis143 skeletal muscle M. gravis1432 sarcolemma1436 myosin

Ig- AGM A G M LIPODYSTROPHY147 lipocytes

Ig- AGM A G M EPIDERMIS1501 desmosomes pemphigus1495 desmoglein 1 pemphigus1496 desmoglein 3 pemphigus1502 epiderm. basal membr. pemphigoid1502 BP180 bullous pemphigoid1502 BP230 bullous pemphigoid135 oral mucosa Behçet’s/ Crohn’s dis.1503 basal membrane (urinary bladder)1509 epidermal keratin191 endomysium GSE, Duhring’s dis.3011 gliadin GSE, Duhring’s dis.1502 herpes gestationis factor1504 melanocytes150h hair follicle

Ig- AGM A G M LIVER, BILIARY DUCTS130 Liver Ab IFT global testing, 6 BIOCHIPs130 Autoimmune Liver Dis. Ab Profile EUROLINE AMA-M2, 3E (BPO), Sp100, PML, gp210, LC-1, LKM-1, SLA/LP, Ro-52

Autoimmune hepatitis (AIH)1302 SLA/LP (soluble liver antigen)1651 F-actin151 ANA (cell nuclei) IF global testing1307 LC-1 (liver cytosol)132 LKM (liver kidney microsomes)1321 LKM-1 ELISA1322 LKM-21323 LKM-31303 ASGPR (asialoglycoprotein receptors)171 ASMA (smooth muscles)1301 LSP (liver-specific protein)1304 LMA (liver cell membrane)

Primary biliary cirrhosis (PBC)162 AMA (mitochondria)1622 AMA-M2 (PDH + BPO)1624 AMA-M4 (sulfitoxidase)1629 AMA-M9 (glycogen phosphorylase)1603 Sp100 (nuclear dots)1608 GP210 (nuclear membrane, lamin)

Primary-sclerosing cholangitis (PSC)121 pANCA (granulocytes)

further antibodies1305 bile ducts1306 bile canaliculi1609 coilin; P80 (few nuclear dots)

Ig- AGM A G M STOMACH, INTESTINE1361 PCA (parietal cells) atroph. gastritis 1361 H+/K+-ATPase ab atroph. gastritis1362 intrinsic factor ab vit. B12 deficiency1366 gastrin (G) cells1391 pancreas acinus cells Crohn’s dis.1391 CUZD1 Crohn’s dis.1392 GP2 Crohn’s dis.2841 Saccharomyces cerev. Crohn’s dis.1392 pankreas secretion Crohn’s dis.135 mouth mucosa Behçet’s/ Crohn’s dis.1381 intestinal goblet cells ulc. colitis121 pANCA (granulocytes) ulc. colitis1382 enterocytes Crohn’s dis. , ulc. colitis191 endomysium GSE, Duhring’s dis.191 transglutaminase GSE, Duhring’s dis.3011 deamidated gliadin (Z-AGFA) GSE192 reticulin GSE, Duhring’s dis.

EXOCRINE GLANDS, PANCREATITIS,Ig- AGM A G M SJÖGREN’S SYNDROME139 exocrine pancreas 1391 pancreas acini1393 pancreas excretory ducts142 salivary glands (parotid gland)1421 parotid gland acini1423 parotid gland excretory ducts141 lacrimal gland

Sjögren’s syndrome151 ANA (cell nuclei) IF global testing1595 SS-A (Ro)1597 SS-B (La)1576 ssDNA (single-stranded DNA)

further antibodies1401 prostate1406 mamma

Ig- AGM A G M ANTIBODIES AGAINST ANIMAL IgG3811 HAMA (human anti-mouse IgG)

Ig- AGM A G M KIDNEY, LUNG120 cANCA IFT* granuloc. Wegener’s dis.121 pANCA IFT* granulocytes vasculitis125 kidney IF global testing1251 GBM ELISA glomerular basal membrane151 ANA (cell nuclei) IF global testing1572 dsDNA IFT1252 TBM (tubular basal membrane)1271 lung alveolar basal membrane

Ig- AGM A G M HEART1627 AMA-M7 (myocard-specific)146 heart muscle1462 heart: intercalated disk1463 heart: myolemma


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Antibodies for Infectious Serology

Grey: standard analyses *) Currently not available as IVD in the European UnionSI I UK A /

Antibodies against

Ig- AGM A G M BACTERIA A-Z219a AÞ pia felis* 219b Bartonella henselae 219d Bartonella quintana 2055 Bordetella parapertussis 2050 Bordetella pertussis 2131 Borrelia afzelii 2132 Borrelia burgd. s. stricto CSF diagnostics2133 Borrelia burgd. (USA) 2134 Borrelia garinii 2092 Campylobacter coli 2091 Campylobacter jejuni 2192 Chlamydia pneumoniae 2191 Chlamydia trachomatis 2040 Diphtheria toxoid 2070 Haemophilus infl uenzae 2080 Helicobacter pylori 2101 Klebsiella pneumoniae 216a Legionella bozemanii 2167 Legionella dumoffi i 2166 Legionella gormanii 2165 Legionella jordanis 2168 Legionella longbeachae 2169 Legionella micdadei 2150 Legionella pneumophila Serotypes ..................2140 Listeria monocytogenes 1/2a 4b2201 Mycoplasma hominis 2202 Mycoplasma pneumoniae2060 Tetanus toxoid 2111 Treponema pallidum CSF diagnostics2205 Ureaplasma urealyticum 2170 Yersinia enterocolitica O:3 O:4 O:6 O:9

Ig- AGM A G M PARASITES A-Z2320 Echinococcus gran. 2231 Leishmania donovani 2261 Plasmodium vivax 2264 Plasmodium falciparum 2410 Toxoplasma gondii Avidity determination

Ig- AGM A G M VIRUSES A-Z2680 Adenovirus type 3 2730 Coxsackievirus type B1 B2 B3 B4 B5 B6 A7 A9 A16 A24 2570 Cytomegalovirus Avidity determination275a Echovirus type 7 2791 Epstein-Barr virus capsid Ag (EBV-CA) Avidity determination2795 Epstein-Barr virus early Ag (EBV-EA)2793 Epstein-Barr virus nuclear Ag (EBNA)2531 HSV-1 2532 HSV-2 2511 HIV-1* 2512 HIV-2* 2536 Human herpes virus 6 (HHV-6) 2691 Infl uenza virus type A H1N1 H3N22692 Infl uenza virus type B 2610 Measles virus CSF diagnostics2630 Mumps virus CSF diagnostics2720 Parainfl uenza virus type 1 2 3 42670 Respiratory syncytial virus (RSV)2590 Rubella virus Avidity determination CSF diagnostics2661 TBE virus 2650 Varicella zoster virus Avidity determination

Ig- AGM A G M FUNGI A-Z2861 Candida albicans 2862 Candida glabrata 2863 Candida krusei 2865 Candida parapsilosis 2864 Candida tropicalis 2841 Saccharom. cerevisiae

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Antibodies for Allergology

Allercoat™ 6 System: Antibodies of class IgE against 600 differentallergens of the areas animal allergens, environmental allergens,food, grasses, herbal and flower pollen, house dust, insects, mites,moulds, parasites, pharmaceutical drugs, trees.

Allergen Profiles: Antibodies of class IgE againstGLOBAL TEST

3840 Determination of total IgE (ELISA)

INHALATION

3110 Allergy Profile Inhalation(g1, g3, g6, g12, t2, t3, t4, t7, w1, w6, w9,d1, d2, e1, e2, e3, m1, m2, m3, m6, CCD)

3110 Allergy Profile Inhalation 2(g6, g12, t2, t3, t4, w6, w9, d1, d2, e1, e2, e3, e6,e82, e84, es4, m1, m2, m3, m6, CCD)

3111 Allergy Profile Pediatric Inhalation(g6, g12, t2, t3, t4, w6, w8, w9, d1, d2, e1,e2, e3, e6, e82, e84, m1, m2, m3, m6, CCD)

3112 Allergy Profile Mediterranean Inhalation(g2, g6, t3, t4, t9, t11, t23, t210, w1, w6, w9, w19,d1, d2, d70, e1, e2, e3, m2, m6, CCD)

3113 Allergy Profile Inhalation "South East Asia"(ts19, t104, t19, t223, gs1, ds1, i6, u134, e1,e2, es172, e6, e71, e82, e84, ms1, ms4, m5,m12, m45, CCD)

3116 Allergy Profile Inhalation "China"(gs23, ts21, t3, t8, t11, t12, t14, t70, ws18, w1, w6,w9, es1, d1, d2, i6, ms5, m1, u73, u80, CCD)

3117 Allergy Profile Inhalation "Middle East"(g1, g6,g12, t2, t3, t7, t9, w1, w6, w8, d1, d2,i6, e1, e84, m1, m2, m3, m5, m6, CCD)

3118 Allergy Profile Inhalation "Gulf"(g6, g12, t2, t3, t7, t9, w1, w6, d1, d2, i6, e1,e2, e3, e17, m1, m2, m3, m5, m6, CCD)

3119 All. Profile Inhalation “Mix-Screen Turkey 1”(ts23, ts24, ts25, gs12, gs15, gs21, ws17, ws18,ws19, ws20, ms11, ms12, CCD)

3119 Allergy Profile Inhalation “Turkey 1”(gs12, gs15, gs21, g12, ts23, ts24, t9, t70, ws18,ws19, ws20, d1, d2, i6, es2, es172, e1, e2, e3, e4,e80, e81, e84, ms11, ms12, m1, m2, m3, m6, CCD)

3119 Allergy Profile Inhalation “Turkey 2”(m1, m2, m3, m6, ds1, i6, e1, e2, e3, e4,e81, e84, CCD)

3120 Allergy Profile Inhalation "India"(g6, g12, g20, t18, w4, w27, w29, ds1, d2, i6, e1, e2,e11, e85, m3, m37, u81, u126, u129, u140, CCD)

FOOD

3410 Allergy Profile Food(f1, f75, f2, f45, f4, f5, f9, f13, f14, f17, f20, f49,f84, f237, f25, f31, f35, f85, f3, f23, CCD)

3410 Allergy Profile Food 2(f1, f75, f2, f78, f4, f5, f14, f10, f13, f17, f20, f49,f84, f95, f25, f31, f35, f85, f3, f23, CCD)

3411 Allergy Profile Food "South East Asia 1"(f1, f75, f2, f4, f9, f10, f14, f13, f17, f63, f64, f83,fs10, fs14, f23, f24, f80, f179, f105, f336, CCD)

3411 Allergy Profile Food "South East Asia 2"(f1, f75, f2, f4, f9, f10, f14, f13, f17, f63, f340, f83,fs10, fs14, f23, f24, f80, f179, f105, f336, CCD)

3414 Allergy Profile Food "China"(f1, f2, f4, f7, f27, f88, fs35, f13, f14, fs40, f25,f292, fs42, f23, f234, f3, f41, f56, fs41, fs77, CCD)

3415 Allergy Profile Food "Middle East"(f1, f75, f2, f78, e204, f4, f14, f45, f13, f17, f20,f33, f49, f92, f25, f31, f85, f48, f88, f89, CCD)

3416 Allergy Profile Food "Gulf"(f1, f75, f2, f105, f4, f14, f45, fs36, f13, f29, f33,f44, f93, f25, f31, f48, f83, f88, f3, f23, CCD)

3417 Allergy Profile Food "Cyprus 1"(f1, f2, f75, f76, f77, f78, f81, f4, f45, f5, f14, f7,f79, f9, f10, f13, f144, f17, f20, f49, CCD)

3418 Allergy Profile Food "Cyprus 2"(f177, f23, f234, f24, f258, f3, f37, f40, f41, f80, f48,f108, f132, f212, f25, f292, f31, f35, f47, f96, CCD)

3419 Allergy Profile Food "Cyprus 3"(f26, f63, f83, f88, f237, f29, f32, f328, f33, f44, f49,f72, f84, f95, f281, f86, f89, f90, f105, f93, CCD)

3420 Allergy Profile Food “Mix Screen Turkey 1”(f245, fs8, fs50, fs38, fs37, fs46, fs47, fs48,fs49, fs45, fs10, fs16, CCD)

3420 Allergy Profile Food “Turkey 1”(f1, f75, f2, f169, f78, f4, f79, f9, f14, f10, f13, f17,f144, u87, f222, f73, f33, f44, f49, f92, f84, f146,f328, f25, f31, f35, f48, f95, f97, f122, f132, fs14,fs10, fs43, f83, CCD)

3420 Allergy Profile Food “Turkey 2”(f3, f21, f206, f437, f438, f436, f71, f177, f324,f27, f83, f88, CCD)

3420 Allergy Profile Food “Turkey 3”(f1, fs51, f14, fx20, f13, fs35, f49, f44, f25, f31,fs10, fs16, CCD)

3421 Allergy Profile Food "India"(f2, f75, f168, f4, f9, f14, f13, f36, f49, f50, f35, f38,f48, f244, f83, f89, f74, f240, f23, f24, CCD)

ATOPY, POLLEN-ASSOCIATEDFOOD ALLERGIES

3710 Allergy Profile Atopy(g6, g12, t3, w6, d1, e1, e2, e3, m2, m6, f1, f2,f3, f4, f9, f14, f17, f31, f35, f49, CCD)

3710 Allergy Profile Atopy 3(g6, t3, t4, w6, d1, d2, e1, e2, e3, m2, m3, f1,f75, f2, f3, f4, f13, f14, f31, f49, CCD)

3711 Allergy Profile Pollen-FoodCross Reactions(g6, t3, w6, f4, f5, f13, f17, f20, f48, f89,f271, f275, f44, f49, f348, f237, f328, f31,f35, f85, CCD)

3712 Allergy Profile Pediatrics(gx, t3, w6, d1, e1, e2, e3, m2, m6, f1, f75, f3, f2,f76, f77, f78, e204, f4, f9, f14, f13, f17, f31, f35,f49, CCD)

3713 Allergy Profile Atopy "China"(ts20, w1, w6, ds1, h1, e1, e2, i6, ms1, u80, f1, f2,f13, f14, f27, f88, fs33, fs34, f23, f234, CCD)

3713 Allergy Profile Atopy "China 3"(ts22, w6, us1, ds1, es1, h1, ms5, f245,fs9, fs43, fs56, fs34, fs44, CCD)

3719 Allergy Profile Atopy “Mix Screen Turkey 1”(hs12, ms1, gs2, ws21, ts26, ts25, fx5, fx20,es5, es6, es172, es2, CCD)

3719 Allergy Profile Atopy “Turkey 1”(d1, m2, es5, g6, t3, w6, f1, f2, f13,f14, f4, fs16, CCD)

INSECT VENOMS

3720 Allergy ProfileInsect Venoms(i1, i3, CCD)


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EUROIMMUN Microplate ELISA


• Polystyrene microplate strips coated with purified, biochemically characterizedantigens are used as solid phase containing bound antigens.

• If the sample is positive, specific antibodies in the diluted serum sample attachto the antigens coupled to the solid phase.

• In a second step, the attached antibodies are detected with peroxidase-labelledanti-human antibodies.

• In a third step, the bound antibodies are made visible using a chromogen/substrate solution which is capable of promoting a color reaction. The intensityof the color produced is proportional to the concentration of antibodies in theserum sample.

• Monospecific ELISA (enzyme immunoassays with a single antigen) provide aquantitative in vitro assay for the detection of antibodies.

• “Profile ELISA” provide a semiquantitative in vitro assay for the detection ofdifferent antibodies on a single microplate strip.

• The solid phase of “Pool ELISA” is coated with an antigen mixture for the semi-quantitative detection of antibodies whose specificity must be subsequentlyinvestigated by monospecific assays.

Reliable and Economical Calibration/Evaluation

• In the case of a quantitative ELISA, calibration is performed using three cali-bration sera.

Calibration serum 1: upper limit of the measurement range

Calibration serum 2: upper limit of the normal range (cut-off value)

Calibration serum 3: negative

• Only three wells are required for calibration, followed by serum samples. Thereis no need to incubate blank values or duplicate determinations.

• Semiquantitative ELISA are performed using only one calibrator.

• The calibration is performed in relative units per milliliter (RU/ml) or, if aninternational reference serum exists, in international units per milliliter (IU/ml).

• Each test can be optionally performed using a positive or negative control serumincluded in the test kit. Kit-specific reference ranges are provided for eachcalibrator and control serum.

• All calibrations can be easily performed with the usual ELISA software.

Easy, Quick and Economical Handling

• Microplate strips containing break-off wells (except Profile ELISA), each markedwith an antigen abbreviation to avoid confusion of wells.

• Reagents ready for use (wash buffer: concentrate). Reagents are color-coded toensure positive identification.

dark red: calibration serum 1 orange: anti-human IgA POD-conj.

red: calibration serum 2 green: anti-human IgG POD-conj.

light red: calibration serum 3 red: anti-human IgM POD-conj.

dark blue: pos. control serum turquoise: anti-human IgGM POD-conj.

green: neg. control serum yellow: anti-human IgAGM POD-conj.

light blue: sample buffer

• The sample buffer for infectious serology ELISA (detection of antibodies of classIgM) already contains an IgG/RF absorbent.

• Several tests can be combined on one and the same microplate, since the incu-bation times (30 min; 30 min; 15 min) are identical for all ELISA. Incubation atroom temperature.

• Compatible with all commercial washer and reader systems.

antigen-coatedmicroplate well


POD-labelledanti-human antibody

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Determination of Low-Avidity Antibodies

• An alternative principle for the serological diagnosis of fresh infections has beenestablished by investigating the antibody avidity.


• To identify low-avidity antibodies in a patient’s serum, two microplate ELISA areperformed in parallel: one test is carried out in the conventional way, the otherone includes urea treatment between incubations with patient’s serum and per-oxidase-labelled anti-human IgG, resulting in the detachment of low-avidityantibodies from the antigens.

• Low-avidity antibodies are present if the ELISA extinction is significantly reducedby urea treatment. For an objective interpretation, the relative avidity index (RAI)can be calculated out of the measured values with and without urea incubation.

• Serum dilution 1 : 100, conjugate class anti-human IgG, POD-labelled.

• 3-point calibration, quantitative (IgG).

• The following test kits for avidity determination are available: Toxoplasmagondii, CMV, rubella virus, VZV, West-Nile virus, EBV-CA.

Avidity of antibodies against EBV-CA (IgG)

Relative Avidity Index (RAI) in %

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EUROIMMUN Microplate ELISA

Antibody Determination in CSF

• Indication: local infections of the brain.

• CSF dilution 1 : 2, serum dilution 1 : 404. Conjugate classes anti-human IgG orIgM, POD-labelled.

• Easy to conduct: ready-for-use reagents.

• 4-point calibration, quantitative. Identical incubation conditions and times (roomtemperature; 60 min / 60 min / 15 min): all EUROIMMUN ELISA for CSF dia-gnostics can be combined without difficulty on one and the same microplate.

• The antibody concentration in the patient’s serum is determined in parallel tothe antibody concentration in CSF on one and the same microplate. The CSF/serum quotient CSQpath.-spec. is calculated from both measured values.

• An intrathecal synthesis of specific antibodies is present if the CSF/serumquotient of the specific antibodies CSQpath.-spec. is significantly higher than theCSF/serum quotient of the whole IgG (CSQtotal) or if necessary the CSQlim.. Therelation of both values indicates the relative CSF/serum quotient CSQrel.(synonym: antibody specificity index, ASI).

• Interpretation of results (according to the recommendations of Prof. Reiber):

CSQrel. < 1,3: standard range

CSQrel. 1,3 – 1,5: borderline range

CSQrel. > 1,5: Indication of pathogen-specific antibody production in the CNS

• For the automatic calculation of the CSQrel. EUROIMMUN provides a specificExcel table free of charge.

• Highest sensitivity, specificity and reproducibility. Antibody concentrations inthe serum and CSF are determined within the linear range of the test.

• The following test kits for CSF diagnostics are available: Borrelia burgdorferi,Toxoplasma gondii, HSV-1, HSV-2, HSV-1/2 Pool, CMV, rubella virus, measlesvirus, mumps virus, VZV, TBE, EBV-CA.

• All test systems for CSF diagnostics can also be used only for serology.

• Perfectly adapted for the automated incubation in incubation devices.

CFS/serum quotient diagram according to Reiberand Lange (1991)

ELISA incubation scheme

Table-based evaluation of the CSQrel.

CSF calibrators CSF serumC SD-AC

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Blood-CSF barrier dysfunction, no Ig production in CNS

Blood-CSF barrier dysfunction, additional Ig production in CNS

Clear Ig production in CNS, no disturbance in blood-CSFbarrier function

Error in blood extraction or analysis


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ELISA Automation Using the EUROIMMUN Analyzers

EUROIMMUN Analyzer I and EUROIMMUN Analyzer I-2P: BroadParameter Spectrum, Proven Reliability, Variable Throughput

• One for all: fully automated processing of all EUROIMMUN ELISA – autoimmunediagnostics, infectious serology and allergology – with only one system

• Flexibility for your benefit: open system with more than 800 validatedEUROIMMUN parameters for serum, plasma and cerebrospinal fluid, over 50 or30 parameters in parallel.

• Convenient, simple and reliable operation: e.g. by scanning QC certificates usinga 2D-hand barcode scanner – ready-for-use reagents and preprogrammed assayprotocols enable you to start immediately.

• Capacity and throughput: quick loading and efficient time management allowprocessing of up to 70 or 50 tests per hour – up to 7 or 3 plates, 180 or 144samples at the start of a run.

• Security for patients: validated test systems and the comprehensive safety kitprovide the basis for reliable diagnostics.

• Reliability and service: instruments and reagents from one manufacturer, quickand targeted support from our personnel for a smooth workflow in yourlaboratory.

Modular System: A Highly Sophisticated Solution

• High convenience, fast and reliable loading through barcode identification ofsamples and reagents: automatic scanning when racks are inserted, reading oflot-specific QC data via 2D hand barcode scanner.

• Dilution area: 288 or 192 dilution positions (Deepwell, 2 ml).

• Liquid level detection (capacitive), multi-shot (dispensing) mode, automatic tipdetection, clot detection.

• Pipetting possible during plate transport due to separation of transport andpipetting unit.

• 4 or 2 incubators with heating and shaking function, 4 or 3 incubators at roomtemperature.

• Standard Windows software: familiar user interface, all relevant statisticalfunctions provided, available in different languages.

• Efficient use and convenient handling of tips and dilution plates throughmemory function.

A Convincing and Reliable Package: EUROIMMUN Analyzer,EUROIMMUN ELISA, EUROIMMUN Service

• Comprehensive test system validation for the EUROIMMUN Analyzer: all para-meters validated in accordance with the 98/79/EC directive and based onEN ISO 13485:2003/CMDCAS.

• All ELISA test systems are manufactured according to the European QualityStandards (IVD).

• National and international conformity (standardisation): CE, IVD, FDA andCMDCAS.

• Programming and set-up of automated system, including introduction to thesystem with customer training, performed by qualified personnel.

• Reliable and fast delivery of consumables and reagents.

• Connection to in-house computer system via communication protocol ASTM.

• Maintenance contract with EUROIMMUN on request.

*) soon available for the EUROIMMUN Analyzer I-2P


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microplate wells coatedwith antigens

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Evaluate: photometric measurementat a wavelength of 450 nm



Incubate: 15 min


stopsolution

Incubating the Microplate ELISA


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EUROASSAY: Line Blot in TITERPLANE™ Technique Format


• Membrane strips coated with thin parallel lines of several purified, biochemicallycharacterized antigens are used as solid phase. The membrane strips are fixedas BIOCHIPs in the fields of microscope slides.


• In a second incubation step, the attached antibodies react with AP-labelled anti-human antibodies.

• In a third step, the bound antibodies are stained with a chromogen/substratesolution which is capable of promoting a color reaction. An intense dark band atthe line of the corresponding antigen appears if the serum sample containsspecific antibodies.

• The microscope slides are incubated using the TITERPLANE™ Technique:samples and reagents are applied to the reaction areas of a reagent tray. Theslides are then placed into the recesses of the reagent tray, where all test stripsof one slide come into contact with the liquids, and the individual reactionsbegin simultaneously.

• Depending on the spectrum of antigens used, it is possible to analyze severalantibodies next to each other and simultaneously under identical conditions.

Easy Handling

• Several serum samples can be analyzed simultaneously on one and the sameslide.

• Total time for performing the EUROASSAY test is about 100 minutes. During thewashing procedure, reagents for the next incubation step can be applied toreagent trays.

• All incubation steps proceed at room temperature. Shaking the slides togetherwith the reagent tray on a circulatory shaker ensures the best possiblesensitivity.

• Low reagent consumption. Only 50 µl each of diluted serum and reagent areneeded per test field.

• Reagents ready for use (wash buffer: concentrate).

Reliable and Simple Evaluation

• Since results are evaluated visually, there is no investment required forphotometers, etc.

• The antigen bands are located at exactly defined positions, which means thatevaluation of the test is much simpler than for Westernblots.

• Correct completion of the individual incubation steps in each test field isindicated by staining of the control band.

• Positive and negative results can be easily and reliably differentiated from eachother. The intensity of the antigen bands correlates with the antibody titer.

• The antigens used are highly pure, mostly isolated by affinity chromatography.The membrane strips do not contain any superfluous proteins which mightcause unspecific positive results.

• The incubated microscope slides can be stored for long periods. Results can beeasily documented.

EUROASSAY Anti-ENA ProfilePlus: detection ofantibodies against SS-A and SS-B in a case ofSjögren’s syndrome.

Controlband


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��

��

��

��

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Incubate: 30 min shaking on acirculatory shaker(300 rpm)


slide

reagent traymembrane strips

diluted samples

washbuffer

enzyme conjugate

chromogen/substratesolution

washbuffer

Pipette: 50 µl per field






Wash: flush with deionizedor distilled water,air dry

Evaluate: visual assessmentof color intensity

Incubating the EUROASSAY (TITERPLANE™ Technique)


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PM-Scl100

Mi-2

Ku

Ro-52

PL-7

Jo-1

PL-12

nRNP/Sm

SSARo-52

SS-B

Sm

Scl-70

PM-Scl

Jo-1

CENP B

PCNA

AMA-M2

Sp100

M2-3E(BPO)

PML

gp210

LKM-1

LC-1

SLA/LP

Ro-52

PM-Scl75

SRP

EJ

OJ


• Membrane strips coated with thin parallel lines of several purified, biochemicallycharacterized antigens are used as solid phase. The membranes are fixed asBIOCHIPs onto synthetic foil.


• In a second incubation step, the attached antibodies react with alkaline-phosphatase-labelled anti-human antibodies.


• Depending on the spectrum of antigens used, it is possible to analyze severalantibodies next to each other and simultaneously under identical conditions.

Easy Handling, Reliable and Simple Evaluation

• A separate membrane strip is incubated for each serum sample.

• Total time for performing the analysis is about 105 minutes.

• The incubation can be automated using the EUROBlotMaster.

• All incubation steps proceed at room temperature.

• The antigen bands are located at exactly defined positions, which means thatthe evaluation of the test is much simpler than for Westernblots.

• Correct completion of the individual incubation steps is indicated by staining ofthe control band on each EUROLINE test strip.

• Positive and negative results can be easily and reliable differentiated from eachother. The intensity of the antigen bands correlates with the antibody titer.

• The antigens used are highly pure, mostly isolated by affinity chomatography.The membrane strips do not contain any superfluous proteins which mightcause unspecific positive results.

• The incubated EUROLINE test strips can be stored for long periods. Results canbe easily documented.

• The program EUROLineScan from EUROIMMUN has been developed to enablequantitative evaluation of EUROLINE test strips, to facilitate management ofdata, and to provide detailed documentation of results. First, the incubatedEUROLINE test strips are scanned using a flatbed scanner. EUROLineScanrecognizes the position of the strips, even if they have been placed inexactly,identifies the bands, and measures their intensity. The results are then savedtogether with the image data. A separate results sheet can be produced for eachpatient.

stain

APsubstrate chromogen

AP




antibody

The EUROLINE: A New Technique for Extensive Antibody Profiles

Incubated EUROLINE test strips (AutoimmuneLiver Diseases Profile, ANA Profile 3, MyositisProfile 3.

ControlControlControl

Rib. P-prot.

Histones

dsDNSNucleos.

AMA M2


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EUROBlotMaster

EUROBlotCamera EUROBlotScanner

EUROLINE Automation Using EUROBlotMaster and EUROLineScan

EUROBlotMaster

• Standardised incubation of immunoblot strips – higher precision and repro-ducibility.

• Automatisation of all EUROIMMUN immunoblot strips (EUROLINE, EUROLINE-WB, Westernblot)

• Over 65 validated parameters available (16 autoantibody, 28 infectious and 21allergy parameters)

• Up to 30 strips per test run

• Easy operation

• Combination of different conjugates/tests in one run

• Walk-away function – fully automated from the start to the end of processingfollowing loading

• Compatible with modern evaluation systems such as EUROBlotCamera andEUROLineScan

Automatic Evaluation of the Results Using EUROLineScan

• For all EUROIMMUN blot systems: EUROLINE, EUROLINE-WB, Westernblot.

• For all areas: autoimmune diagnostics, infectious serology and allergology.

• EUROBlotCamera: digitalisation of strips while in the incubation tray.

• EUROBlotScanner: digitalisation of strips using flatbed scanner.

• Fully automated identification, quantitation and assignment of bands.

• Option to modify results (changes are automatically documented).

• Complete results obtained just a few minutes after finishing the incubation.

• Fully automated administration and documentation of extensive individual data.

• Electronic archiving of all images and data (avoids the need to store potentiallyinfectious blot strips).

• Online connection to laboratory software.

• Network compatible.


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p 83

p 39, Bmp Ap 41, Flag.

p 25, Osp C

p 21

p 30p 31, Osp A

p 19

p 17

EURO

LINE

-WB

Borre

liaWesternblot/EUROLINE-WB: Reliable Differentiation of Antibodies Present


• Membrane strips containing electrophoretically separated antigen extracts areused as solid phase. The position of the proteins depends on their respectivemolecular masses.

• If the sample is positive, specific antibodies in the diluted serum sample attachto the antigens coupled to the membrane.

• In a second incubation step, the attached antibodies react with AP-labelled anti-human antibodies.


• Evaluating the band patterns on the incubated membrane strips involvesdifferentiating non-specific from specific antibodies. The number and intensityof the specific bands is decisive for the result “positive/negative“.

stain

AP

substratechromogen

AP




antibody

EUROLINE-WB: detection of antibodies againstBorrelia.

Control band

Alignment bar

Easy Handling, Reliable Evaluation and High Diagnostic Sig-nificance

• A separate membrane strip is incubated for each serum sample.

• Total time for performing the Westernblot test is about 115 minutes.

• All incubation steps proceed at room temperature.

• The bands are assigned according to a lot-specific evaluation matrix provided. Aseparate lot is issued for each electrophoresis gel, helping to avoid errors in theassignment of the bands.

• Every test kit contains a membrane strip of the same lot incubated with apositive reference serum. Therefore, there is no need to incubate a positivecontrol serum.

• The membrane strips are pre-numbered to prevent confusion. Laboriouslabelling is not necessary.

• Correct completion of the individual incubation steps for each membrane strip isindicated by staining of the control band at the bottom of the strip.

• Positive and negative reactions can be easily and reliably differentiated fromeach other. The intensity of the antigen bands correlates with the antibody titer.

• The Westernblot is the method of choice when the objective is to confirm ordifferentiate positive results obtained in a screening test (indirect immuno-fluorescence or microplate ELISA).

• EUROLINE-WB is a combination of westernblot and line blot techniques.Proteins from a whole antigen extract are electrophoretically separatedaccording to molecular mass and transferred onto a nitrocellulose membrane.Highly purified native or recombinant antigens are then printed as lines onto thewesternblot strips (EUROLINE membrane chip).

• The program EUROLineScan from EUROIMMUN has been developed to enablequantitative evaluation of Westernblot/EUROLINE-WB test strips, to facilitatemanagement of data, and to provide detailed documentation of results. First,the incubated Westernblot/EUROLINE-WB test strips are scanned using a flatbedscanner. EUROLineScan recognizes the position of the strips, even if they havebeen placed inexactly, identifies the bands, and measures their intensity. Theresults are then saved together with the image data. A separate results sheetcan be produced for each patient.

VlsE antigen on EURO-LINE membrane chip


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3x

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3x

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Incubate: 5-15 min shaking, de-pending on test system

Aspirate off:

membrane strip

diluted samples

buffer

enzyme conjugate

chromogen/substrate solution

Pipette: 1.5 ml per channel


Wash: 1.5 ml buffer,5 min incubation,aspirate off

incubation channel

buffer

Incubate: 30 min shaking




Wash: 1.5 ml buffer,5 min incubation,aspirate off


Wash: rinse with distilledwater, aspirate off

Evaluate: with EUROLineScan orvisual assessment

buffer

Incubating the EUROLINE/Westernblot/EUROLINE-WBusing the EUROBlotMaster or manually on a rocking platform

Applicable for most EUROLINE/Westernblot/EUROLINE-WB test kits


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125I125I

125I

EUROIMMUN Radioimmunoassays (RIA/IRMA)

Test principle RIA (precipitation techniques)

• In the first incubation step patient sera are incubated with 125I-labelled antigen inpolystyrene tubes. Any specific antibodies in the sera bind to the antigen.

• In the second incubation step the antigen-antibody complexes are precipitatedusing a precipitation agent.

• The precipitate is washed with buffer. After centrifugation and decanting of thesupernatant, the radioactivity in the precipitate is counted using a gammacounter. The intensity of the radioactivity is proportional to the concentration ofspecific antibody in the patient serum.

• The antibody concentration is evaluated quantitatively using a calibration curve.

Test principle RIA (coated tubes)

• RIA tests (coated tubes) are competitive ligand assays for antibody and antigendeterminations.

• The intensity of radioactive radiation is inversely proportional to theconcentration of specific antibodies or antigens in the sample.

• The quantitative evaluation of the antigen/antibody concentration is carried outusing a calibration curve.

Test principle IRMA (antigen determination)

• With this test principle, monoclonal antibodies which are bound directly orindirectly to the inner wall of polystyrene tubes are used.

• During the first incubation step, the patient sera to be investigated are incubatedwith the monoclonal 125I-labelled antibodies in the coated tubes.

• The antigen in the sample is bound by the immobilised antibodies and by the125I-labelled antibodies. This results in a solid-phase bound sandwich complex.

• The unbound 125I-labelled antibodies are removed by washing and subsequentlydecanting. The intensity of radioactive radiation is proportional to the concen-tration of antigens in the patient serum.

• The quantitative evaluation of the antigen concentration is carried out using acalibration curve.

Simple and economical handling, reliable analysis

• Simple test procedure.

• Synchronous processing of samples, including different tests in parallel.

• Ready-to-use reagents (possible exceptions: tracer, precipitation reagents).

• Different test formats for small and large sample series.

• Because of the large measurement range of EUROIMMUN RIA, furthermeasurements with other sample dilutions are generally not necessary.

• Simple evaluation of test results.

• Each test can be optionally evaluated with controls which are supplied in thetest kit. Test kit-specific reference ranges are given for all controls.

• EUROIMMUN radioimmunoassays show the following analytical characteristics:

– High analytical specificity.

– High detection sensitivity.

– High clinical sensitivity and specificity.

– Good reproducibility.

precipitationagent

specific human antibodyradioactively

labelledantigen

(“tracer”)

radioactivelylabelledantibody

analyte

antibody

solid phase(tube surface)


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EUROIMMUN PRODUCTS FOR THE DETERMINATION OF AUTOANTIBODIES


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Autoantibodies against Cell Nuclei (ANA)

Indirect Immunofluorescence Test: EUROPLUS™ ANA Mosaic 20

• Screening test for the detection of antibodies against cell nuclei (ANA).

• Indications: rheumatic diseases.

• Initial dilution 1 : 100; conjugate class anti-human IgG, FITC-labelled.

• Using HEp-2 cells many antibodies against cell nuclei can be analyzed, e.g. anti-bodies against DNA, histones, RNA, nRNP, Sm, SS-A, SS-B, nuclear dots, centro-meres, nuclear membrane, nucleoli (PM-Scl, fibrillarin, RNA polymerase I, NOR),Scl-70, cyclin I and II, spindle fibers, midbody, centrioles.

• In addition, cytoplasmic autoantibodies are identified with HEp-2 cells:antibodies against ribosomes, Jo-1, mitochondria, Golgi apparatus, actin etc.

• The primate liver permits the verification of results between both substrates, makesthe pre-differentiation of a large number of ANA possible, and helps to establishtiter levels. Moreover, the primate liver often contains additional antigens, allowingthe identification of further autoantibodies: antibodies against LMA, LSP, endo-mysium, bile ducts and endothelium cells, as well as cANCA und pANCA.

• The EUROPLUS™ system is a monospecific test that can be used to confirm thepresence of autoantibodies against cell nuclei and cytoplasm with one and thesame test kit. The following antigens are currently available as EUROPLUS™BIOCHIPs: SS-A, SS-B, nRNP/Sm, Sm, Scl-70, Jo-1, ribosomal P-proteins.

Order No. FormatsFA 1510-####-20 G page 126

Order No. FormatsFA 1522-#### G page 128

Order No. FormatsDA 1590-####-1 G page 79

EUROASSAY: Anti-ENA ProfilePlus

• Differentiation of anti-nuclear antibodies (ANA).


• Serum dilution 1 : 100; conjugate class anti-human IgG, AP-labelled.

• 6 relevant anti-nuclear antibodies against “extractable nuclear antigens“ (ENA)can be detected simultaneously and monospecifically: antibodies againstnRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1.

• Native antigens, purified by affinity chromatography.

• On request EUROASSAY can be produced with special antigen combinations,for example, with dsDNA, histones, nucleosomes, PM-Scl, nRNP/Sm, Sm, SS-A,Ro-52, SS-B, Scl-70, Jo-1, ribosomal P proteins, centromere protein B, M2, M4,M9, SLA/LP, LC-1, LKM-1.

HEp-2010: antibodies against spindle fibers.

Incubated EUROASSAY Anti-ENA ProfilePlus.

Indirect Immunfluorescence Test: Innovative Cell Line from EURO-IMMUN, HEp-20-10

• Screening test for detection of antibodies against cell nuclei.



• Compared to standard HEp-2 cells, HEp-20-10 cells demonstrate 10-fold moremitotic cells. Antibodies against mitotic-specific structures (centromeres, spindlefibers, midbody, centrioles, NOR) can be more easily identified than with con-ventional preparations.

• At the same time, the cell line HEp-20-10 offers the full antigen spectrum for cellnuclei antibody diagnostics.

• The BIOCHIP with HEp-20-10 can be supplemented with additional substrates,for example, primate liver (ANA; Order No. FA 1512-####-1 G) as well as ratkidney and rat stomach (Order No. FA 1802-####-3 G).

EUROPLUS™ ANA Mosaic 20 (HEp-2 cells, pri-mate liver, SS-A+SS-B BIOCHIPs, rib. P-prot.+Jo-1BIOCHIPs: antibodies against SS-A/SS-B.


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iesnRNP/Sm

Sm

SS-BScl-70

Jo-1

Sm B/B’

Rib.-P

RNP A

RNP 70Ku

CENP B

Ro-52

SS-A

PM-Scl

SS-A

CENP B

AMA M2

Ro-52

PCNA

Mi-2

Ku

Jo-1

PL-7

SRP

EJ

PM-Scl100

PM-Scl75

PL-12

OJ

Ro-52

Incubated EUROLINE ANA Profile 3.

EUROLINE: ANA Profile 3

• Differentiation of antibodies against cell nuclei (ANA).

• Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’ssyndrome, progressive systemic sclerosis, poly/dermatomyositis, PBC.


• With the EUROLINE ANA-Profile 3, fifteen autoantibodies can be determined:antibodies against nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1,centromere protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal P-proteins, AMA M2.

• Antibodies against SS-A are characteristic markers for SLE and Sjögren’ssyndrome. In contrast, antibodies against Ro-52 also occur in patients with otherautoimmune diseases.

• Native antigens, purified by affinity chromatography (exception: centromereprotein B, PM-Scl, Ro-52, PCNA).

• Further antigen combinations: page 80.

• Test strips can be automatically incubated and evaluated using the systemsEUROBlotMaster und EUROLineScan (see page 27).

EUROLINE-WB: HEp-2 Cell Antigens plus SS-A, Ro-52 and CENP B

• Differentiation of antibodies against cell-nuclear and cytoplasmic antigens.

• Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’ssyndrome, progressive systemic sclerosis, poly/dermatomyositis, PBC.

• EUROLINE-WB is a combination of westernblot and line blot techniques. Proteinsfrom a whole antigen extract of HEp-2 cells are electrophoretically separatedaccording to molecular mass and transferred onto a nitrocellulose membrane. Amembrane chip coated with highly purified native SS-A, recombinant Ro-52 andrecombinant CENP B is then added to the westernblot strips.

• Antibodies against SS-A are characteristic markers for SLE and Sjögren’ssyndrome. In contrast, antibodies against Ro-52 also occur in patients with otherautoimmune diseases. EUROLINE-WB contains both antigens next to each otherat defined positions, in addition to the complete HEp-2 antigen spectrum of theWesternblot. The use of native SS-A increases the sensitivity, since 37% of anti-bodies against SS-A do not show any reaction with the denatured antigen fromthe Westernblot

• Serum dilution 1 : 50, conjugate class anti-human IgG, AP-labelled.

• Antigens: SDS extract from HEp-2 cells (whole antigen), highly purified nativeSS-A from calf thymus, recombinant Ro-52 and CENP B.

Order No. FormatsDL 1590-1601-3 G page 80

Order No. FormatsDW 1520-1601-3 G page 83

Incubated EUROLINE-WB HEp-2 Cell Antigens plusSS-A, Ro-52 and CENP B.


histones

dsDNAnucleos.

rib. P-prot.

control

native SS-Arec. Ro-52

rec. CENP B

EUROLINE: Myositis Profile 3

• Differentiation of myositis-associated antibodies against cell-nuclear andcytoplasmic antigens.

• Indications: poly/dermatomyositis.


• With the EUROLINE Myositis Profile 3, eleven autoantibodies can be determined:antibodies against Mi-2, Ku, PM-Scl100, PM-Scl75, Jo-1, SRP, PL-7, PL-12, EJ, OJand Ro-52.



Incubated EUROLINE Myositis Profile 3.

control


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Microplate ELISA: ANA Screen, Anti-ENA PoolPlus

• Screening test for predifferentiation of antibodies against cell nuclei (ANA) andcytoplasm components.

• Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’ssyndrome, progressive systemic sclerosis, polymyositis/dermatomyositis.


• One microplate well incubated per patient.

• 1-point calibration, semiquantitative.

• Native antigens (exception: centromere, recombinant).

• The ANA Screen ELISA supplements the gold standard immunofluorescence. Itis based on a mixture of 10 highly purified antigens, which provide highersensitivity and specificity than the undefined cell extracts used by othermanufacturers.

• Two ELISAs with different antigen combinations, adapted to particularindications or for follow-up of immunofluorescence patterns, are available.

Order No. FormatsEA 1590-9601-8 G page 87


Order No. FormatsEA ####-9601 G page 87

Microplate ELISA: SLE Profile 1/2, Anti-ENA ProfilePlus 1/2

• Differentiation of antibodies against cell nuclei (ANA) and cytoplasm com-ponents.

• Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’ssyndrome, progressive systemic sclerosis, polymyositis/dermatomyositis.

• Serum dilution 1 : 200; conjugate class anti-human IgG, POD-labelled.

• 8 or 6 relevant antibodies can be detected simultaneously.

• 1-point calibration, semiquantitive. Calibrator pool and negative controls eachon a separate microplate strip (SLE Profiles and Anti-ENA ProfilePlus 2) or onthe same microplate strip as the patient serum.

• Native antigens (exception: Ro-52, centromere and PM-Scl, recombinant).

• In total 4 different ELISAs with different antigen combinations, adapted toparticular indications or for follow-up of immunofluorescence patterns, areavailable.

Microplate ELISA: ANA Single-Antigen ELISAs

• Differentiation of antibodies against cell nuclei (ANA) and cytoplasm com-ponents.



• Antibodies against cell nuclei components can be determined quantitatively inRU/ml.

• 3-point calibration, quantitative.

• Identical incubation conditions and times: all single-antigen tests can be com-bined with each other on one microplate.

• Native antigens (exceptions: centromere and PM-Scl, recombinant).

• Single-antigen ELISAs available for detection of antibodies against cell nucleiand cytoplasm antigens: ssDNA, nucleosomes, dsDNA, histones, ribosomal Pproteins, PM-Scl, nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, centromere.

Incubated ELISA ANA Screen (antigen mixture ofdsDNA, histones, nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, ribosomal P-proteins, centromere).

Incubated ELISA Anti-ENA ProfilePlus 2(antigens: ribosomal P-proteins, nRNP/Sm, Sm,SS-A, SS-B, Scl-70, Jo-1, centromere).

Incubated ELISA Anti-SS-A, Anti-SS-B.


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Crithidia luciliae: antibodies against dsDNA.

Incubated ELISA Anti-dsDNA-NcX.

RIA Anti-dsDNA.

Order No. FormatsFA 1572-#### page 128

Order No. FormatsEA 1572-9601 G page 87

Order No. FormatsRA 1571-0001 page 89

Indirect Immunofluorescence Test: Crithidia luciliae

• Detection of antibodies against dsDNA.

• Indication: lupus erythematosus disseminatus.

• Initial dilution: 1:10, conjugate class anti-human IgG, FITC-labelled.

• Animal pathogenic haemoflagellates of Crithidia luciliae are used for the de-tection of autoantibodies against double-stranded, native DNA (dsDNA, nDNA)with indirect immunofluorescence. These protozoa possess a giant mitochon-drion containing dsDNA (kinetoplast) that, in general, does not show any of theother antigens present in the cell nuclei. Antibodies reacting with the kinetoplastare therefore only directed against dsDNA.

• Alongside the conventional CLIFT, which shows a particularly high diseasespecificity, EUROIMMUN has developed an Anti-Crithidia luciliae sensitive IFT(order no. FA 1572-####-1), which is comparable in sensitivity to the Anti-dsDNA-NcX ELISA and the Farr assay. However, despite comparable sensitivities, theassays identify different patients. To increase the serological hit rate differenttest systems are often combined.

Microplate ELISA: Anti-dsDNA-NcX

• Monospecific detection of antibodies against dsDNA.

• Indication: lupus erythematosus disseminatus.

• Serum dilution 1: 200, conjugate class anti-human IgG, POD-labelled.

• Antibodies against dsDNA can be determined quantitatively in IU/ml.


• Antigen: double-stranded DNA, complexed with nucleosomes (NcX).

• Due to good sensitivity and specificity, the Anti-dsDNA-NcX ELISA stands out byhigh diagnostic efficiency. High concentrations of autoantibodies against dsDNAin the ELISA are considered to be a reliable marker for the diagnosis orprognosis of SLE. Individual changes in the dsDNA antibody concentrationcorrelate with the activity of the disease and can be used for monitoring thedevelopment of the disease in SLE patients. In cases of immunosuppressivetherapy or clinical remission dsDNA antibodies cannot be detected with theELISA anymore.

Anti-dsDNA RIA by Farr

• Monospecific detection of antibodies against dsDNA.

• ndication: lupus erythematosus disseminatus.

• Use of undiluted samples.

• Antigen: 125I-labelled dsDNA from plasmid DNA.

• The Farr radioimmunoassay has always been of great importance. On the whole,it has the same specificity as the immunofluorescence test and the samesensitivity as the ELISA. Apparently, its well-known high diagnostic efficiency isbased on the fact that only the fraction of the anti-dsDNA antibodies which isable to form bigger precipitating immune complexes with circulating DNA inliquid phase contributes to the measuring signal. The principle of the Farr testreflects, so to speak, the significant step in the pathomechanism of SLE: theformation of appropriate immune complexes, deposits of which build up in thejoints, kidneys, liver and other organs.

Autoantibodies against Double-Stranded DNA (dsDNA)


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Order No. (Anti-CCP) FormatsEA 1505-9601 G page 87

Antibodies against cyclic citrullinated peptides (CCP): An ELISA for specifi c diagnosis of rheumatoid arthritis

The amino acid citrulline Principle of the anti-CCP ELISA

colourlesschromogen

POD

stain

POD

human antibodyagainst CCP

peroxidase-labelled anti-human antibody

synthetic CCP

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affect-ing around 1% of the world population. It is characterised by infl ammation of the syno-vial membrane, which spreads symmetrical-ly from the small to the large joints. Initial symptoms include painful swelling of Þ nger joints with morning stiffness in the joints. Early diag nosis and immediate commence-ment of suitable therapy is necessary to keep the disease under control.

The most commonly performed serological test in suspected RA cases was until now the determination of rheumatoid factors (RF). These are antibodies (predominantly of class IgM) which react with gamma globulins and occur in 60-80% of RA patients. RF are a sen-sitive but not very specifi c marker for RA, since they also occur in healthy individuals and in patients with various infections or other autoimmune diseases (systemic lupus erythematosus, Sjögren’s syn drome, sclero-derma and others).

40-60% of RA patients also exhibit auto-anti bodies against epidermal fi l ag grin1 (RA

keratin, anti-pe ri nu clear fac tor) in their se-rum. Fil ag grin is a protein of the epi dermis, which links keratin fi laments to one another. Autoanti bodies against fi laggrin are detected by indirect immuno fl uor escence: the antigen substrate rat oesophagus shows staining of the stratum corneum (RA keratin) on the luminal side; anti-perinuclear factors (APF) are apparent in the cyto plasmic inclusion bodies of human epithelial cells of the oral mucosa.

In recent years it has been shown that the rare amino acid citrulline, which is present in fi laggrin, is a substantial component of the antigenic epitope. Enzyme immunoassays which use synthetic citrullinated peptide as the target antigen offer a useful alter-native to indirect immunofl uorescence2. A direct comparison study demonstrated that the sensitivity can be increased from 49% to 68% by using cyclic citrullinated peptide instead of linear citrullinated peptide as an ELISA substrate3. Antibodies against cyc li c

citrulli nated pep tides (CCP) are a new and highly specifi c marker for RA.

An ti bodies against CCP are predominantly of class IgG and have a specifi city of 98% for RA. They are observed very early in the disease course and have a high predictive value: patients with anti-CCP antibodies develop signifi cantly more radiologically detectable joint damage than anti-CCP-negative patients4. Antibodies against CCP possess a much higher specifi city than RF (anti-CCP: 97%, RF: 62%) with the same sen-

sitivity (anti-CCP: 79%, RF: 78%)5. They can be detected in early stages of the disease in 79% of patients.

EU ROIMMUN offers an innovative micro-

plate ELISA for quantitative deter min ation of autoantibodies against CCP. Diluted patient sera are incubated in wells coated with syn-thetic cyclic citrullinated peptides (second gener ation). Specifi c antibodies in the serum bind to the immobi lised antigen and cause a photo metric colour reaction by means of an enzyme-coupled secondary antibody. Five

Anti-CCP ELISA

NH

O NH2

O

N

H

NH

H2N+ NH2

O

N

H

Peptidylarginine-

deiminase (PAD)

Ca2+

L-arginine L-citrulline

calibration sera ensure reliable measure-ment of antibody concentrations. The EURO-IMMUN Anti-CCP ELISA is a highly specifi c and sensitive sero logical test system for the diagnosis of RA.

1) Nogueira et al., Ann. Rheum. Dis. 60: 882 (2001)2) Schellekens et al., J. Clin. Invest. 101: 273-281 (1998)3) Schellekens et al., Arthritis Rheum. 43: 155-163 (2000)4) Kroot et al., Arthritis Rheum. 43: 1831-1835 (2000) 5) Vasishta, Am. Clin. Lab. 21: 34-36 (2002)

Panel nAnti-CCP

positive

Sensitivity RA 419 329 (78.5%)

Asymptomatic blood donors

400 2 (0.5%)

Psoriatic arthritis 28 0

Other arthritides 35 3 (8.6%)

Systemic lupus erythematosus

108 3 (2.8%)

Sjögren‘s syndrome 106 2 (1.9%)

Scleroderma 98 3 (3.1%)

Autoimmune thyroiditis

159 4 (2.5%)

Wegener‘ granulomatosis

25 1 (4.0%)

Anti-parvovirus B19 positive

126 3 (2.4%)

Viral hepatides 54 0

Anti-HIV positive 5 0

Tuberculosis 10 0

Specifi city RA 1154 21 (98.2%)

Autoantibodies against CCP and Sa

Microplate ELISA: Anti-CCP, Anti-Sa

• Screening test for the specific determination of autoantibodies against cycliccitrullinated peptides (CCP) and citrullinated Sa.

• Indication: rheumatoid arthritis (RA).


• Antibodies against CCP and Sa can be determined quantitatively in RU/ml.Optional reference control for the determination of ratio values.

• Antigen: synthetic cyclic citrullinated peptides (CCP, second generation),citrullinated Sa.

Antigen Order No.

CCP EA 1505-9601 G

Sa EA 151a-4802 GIncubated ELISA Anti-CCP, Anti-Sa.


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Autoantibodies against Mitochondria (AMA)

Indirect Immunofluorescence Test: EUROPLUS™ Rat Kidney andM2-3E BIOCHIPs

• Screening test for the detection of antibodies against mitochondria (AMA) in-cluding simultaneous confirmation of the subtype AMA M2.

• Indication: primary biliary cirrhosis (PBC).

• Initial dilution 1 : 100; polyvalent conjugate anti-human IgAGM, FITC-labelled.

• Rat kidney is the standard substrate for detecting anti-mitochondrial antibodies.Nine AMA types (M1 to M9) can be differentiated.

• The BIOCHIP coated with M2-3E permits monospecific confirmation ofantibodies against the native pyruvate dehydrogenase complex and therecombinant M2 fusion protein (BPO) in one single test procedure, thus a PBCcan be diagnosed serologically with confidence.

• This BIOCHIP Mosaic™ can be supplemented as required using additionalsubstrates, e.g. HEp-2 cells (ANA, nuclear dots), rat liver (liver-kidney micro-somes, LKM) or rat stomach (ASMA).

Rat kidney and M2-3E BIOCHIP: antibodiesagainst mitochondria (AMA).

EUROASSAY: AMA Profile M2, M4, M9

• Differentiation of mitochondrial antibodies (AMA).


• Serum dilution 1 : 100; conjugate class anti-human IgGM, AP-labelled.

• 3 relevant mitochondrial antibodies can be detected simultaneously and mono-specifically: antibodies against M2, M4, M9.

• Native antigens: pyruvate dehydrogenase complex (M2), sulfite oxidase (M4),glycogen phosphorylase (M9).

Anti- Associated diseases

M2 Primary biliary cirrhosis (high titers), other chronic liver diseases

M4 Primary biliary cirrhosis

M9 Early phase of primary biliary cirrhosis Incubated EUROASSAY AMA Profile M2, M4, M9.

Microplate ELISA: Anti-M2-3E

• Differentiation of mitochondrial antibodies (AMA).



• Antibodies against M2 can be determined quantitatively in RU/ml.

• Antigen: native pyruvate dehydrogenase complex plus recombinant M2 fusionprotein (BPO) containing the immunogenic domains of the E2 subunits of PDH,BCOADH and OGDH.

Incubated ELISA anti-M2-3E.

Order No. FormatsFA 1620-####-3 page 129

Order No. FormatsDA 1620-####-1 O page 80



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Indirect Immunofluorescence Test: Liver Mosaic 8

• Screening and differentiation test for the detection of liver-specific antibodies,antibodies against mitochondria (AMA), antibodies against cell nuclei (ANA),antibodies against smooth muscles (ASMA), F-actin and other autoantibodies.

• Indications: autoimmune hepatitis, primary biliary cirrhosis, rheumatic diseases.


• The BIOCHIP Mosaic™ consists of 6 substrates: human epithelial cells (HEp-2),primate liver, rat kidney, rat liver, rat stomach, VSM47. Thus, a broad spectrumof antigens is present, allowing not only targeted serological diagnoses, butalso frequently yielding additional results with clinical relevance.

• Antibodies against cell nuclei (ANA) can be particularly well demonstrated usingHEp-2 cells and primate liver, and are identified according to their fluorescencepatterns. However, they also stain the cell nuclei of the other tissues more orless intensely. Clinical significance: rheumatic diseases, primary biliary cirrhosis(antibodies against nuclear dots).

• With primate liver, several liver-specific autoantibodies can be investigated e.g.antibodies against liver cell membrane (anti-LMA) and liver-specific protein(anti-LSP). Clinical significance: autoimmune hepatitis.

• Antibodies against mitochondria (AMA) show a granular cytoplasmic fluo-rescence on all 6 substrates. With the standard substrate rat kidney, the proximaland distal tubule cells fluoresce equally. Clinical significance: primary biliarycirrhosis.

• Autoantibodies against liver-kidney microsomes (anti-LKM) react with rat liverand rat kidney (see below). The other substrates are essentially negative.

• In the case of autoantibodies against smooth muscles (ASMA), the tunicamuscularis, the lamina muscularis mucosa as well as the interglandular con-tractile fibrils fluoresce on the rat stomach. ASMA directed against the targetantigen F-actin furthermore react with the cytoskeleton of HEp-2 cells and thebile canaliculi of primate liver. The substrate VSM47 reacts very specifically,showing a filamentous, needle-like fluorescence. Clinical significance:autoimmune (lupoid) chronic active hepatitis.

• The BIOCHIP Mosaic™ can be supplemented as required with additional sub-strates, e.g. Crithidia luciliae (antibodies against dsDNA), musculus iliopsoas(antibodies against skeletal muscles), heart (antibodies against striated muscles,antibodies against intercalated disks, AMA M7), different EUROPLUS™ sub-strates (AMA-M2-3E, Sp100, gp210, PML, SLA/LP, LC-1, LKM).

HEp-2 cells: anti-nuclear dots. Primate liver: anti-LSP. Rat kidney: AMA. Rat liver: ANA. Ratstomach: ASMA. VSM47: Anti-actin.

Indirect Immunofluorescence Test: BIOCHIP Mosaic™ Rat Liver/Rat Kidney (Liver Mosaic 1)

• Specific detection of antibodies against liver-kidney microsomes (anti-LKM).

• Indications: autoimmune hepatitis, often associated with extrahepaticsyndromes such as arthralgias, glomerulonephritis, vitiligo and chronicinflammatory bowel diseases.


• Autoantibodies against liver-kidney microsomes react with rat liver and generatea smooth staining in the cytoplasm of the hepatocytes.

• In rat kidney, particularly in the cortex area, a fine granular fluorescence of theproximal tubules – recognizable by the luminal brush border – is visible. Thedistal tubules are negative. The fluorescence intensity of the liver cells isnormally stronger than that of the proximal renal tubules.

• The differentiation between autoimmune hepatitis and virus-induced hepatitiscan additionally be accomplished by investigating the appropriate viralparameters.

Rat liver and rat kidney: antibodies against liver-kidney microsomes (anti-LKM).



Autoantibodies against Liver Antigens


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3E (BPO)

Sp100

PML

LKM-1

gp210

LC-1

SLA/LP

Ro-52

EUROLINE: Profile Autoimmune Liver Diseases

• Differentiation of antibodies in autoimmune liver diseases.

• Indications: autoimmune hepatitis, primary biliary cirrhosis, overlap syndromes.


• With the EUROLINE Profile Autoimmune Liver Diseases, nine autoantibodies canbe determined: antibodies against AMA M2, M2-3E (BPO), Sp100, PML, gp210,LKM-1, LC-1, SLA/LP and Ro-52.


• Further antigen combinations on page 79.

Anti- Associated Diseases

M2, Sp100, PML, gp210 Primary biliary cirrhosis

LKM-1, SLA/LP, LC-1 Autoimmune hepatitis

Ro-52 Autoimmune hepatitis, rheumatic diseases

Incubated EUROLINE Profile Autoimmune LiverDiseases.

EUROASSAY: Liver Profile(Anti-M2, -LKM-1, LC-1, -SLA/LP)

• Determination of mitochondrial antibodies AMA M2, antibodies against liver-kidney microsomes type 1 (LKM-1), antibodies against liver cytosolic antigentype 1 (LC-1), as well as of antibodies against soluble liver antigen/liver-pancreasantigen (SLA/LP).

• Indication: autoimmune liver diseases.


• Antibodies against M2, LKM-1, LC-1 and SLA/LP can be detected simultaneouslyand monospecifically.

• Antigens: pyruvate dehydrogenase complex (M2, native), cytochrome P450 IID6(LKM-1, recombinant), formiminotransferase-cyclodeaminase (LC-1, recombi-nant) and soluble liver antigen/liver-pancreas antigen (SLA/LP, recombinant). Incubated EUROASSAY M2, LKM-1, LC-1, SLA/LP.

Microplate ELISA: Anti-SLA/LP, Anti-LC-1, Anti-LKM-1

• Monospecific determination of antibodies against soluble liver antigen/liver-pancreas antigen (SLA/LP), cytosolic liver antigen type 1 (LC-1) and liver-kidneymicrosomes type 1 (LKM-1).

• Indication: autoimmune hepatitis.


• 3-point calibration, quantitative (exception: Anti-LC-1, semi-quantitative).

• Identical incubation conditions and times: all tests can be combined withoutdifficulty on one and the same microplate.

• Recombinant antigens: soluble liver antigen/liver-pancreas antigen (SLA/LP),formiminotransferase-cyclodeaminase (LC-1) and cytochrome P450 IID6 (LKM-1).The corresponding human cDNA was expressed in E. coli (SLA/LP) or insectcells (LC-1, LKM-1). Incubated ELISA Anti-SLA/LP, Anti-LC-1, Anti-LKM-1.


Order No. FormatsDA 1300-1003-3 G page 79

Order No. (Anti-SLA/LP) FormatsEA 1302-9601 G page 86

Autoantibodies against Liver Antigens

AMA M2

control


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Autoantibodies against Thyroid Gland Antigens / Antigen Detections

Indirect Immunofluorescence Test: EUROPLUS™ Thyroid Gland(unfixed) and Thyroglobulin

• Detection of antibodies against thyroid gland antigens.

• Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis.


• Using unfixed thyroid tissue, two important thyroid-specific antibodies can befound: Autoantibodies against thyroid microsomes (MAb) give a granularstaining in the cytoplasm of the follicle epithelium (target antigen: thyroidperoxidase, TPO). Autoantibodies against thyroglobulin (TAb) react with thecolloid of all follicles of the thyroid tissue and cause a reticular fluorescencepattern.

• With the thyroglobulin-coated BIOCHIP, autoantibodies against thyroglobulin(TG) can be confirmed monospecifically in one and the same test procedure.

• This BIOCHIP Mosaic™ can be supplemented as required with further substrates,e.g. rat kidney, to achieve a differentiation of antibodies against thyroid microso-mes from mitochondrial antibodies (AMA). For a serological diagnosis of auto-immune polyendocrinopathies, BIOC

Thyroid gland, unfixed and thyroglobulinBIOCHIP: antibodies against thyroid microsomesand thyroglobulin.

Radioimmunoassays (RIA/IRMA): Thyroid Specific Autoantibodies,Antigens and Hormones

• Monospecific detection of autoantibodies against thyroglobulin (TG), thyroidperoxidase (TPO) and thyrotropin receptor (TSH-R).

• Specific detection of the thyroid antigen thyrotropin and the hormones freetriiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), calcitonin.

• Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis, medullarythyroid carcinoma, thyroidal C-cell hyperplasia, therapy controls in hyper- andhypothyrosis.

• Serum dilutions: 1:50 for anti-TG and anti-TPO (magnetic), 1:20 for anti-TG andanti-TPO (precipitation), undiluted for all remaining test kits.

• 5-point to 8-point calibration (quantitative).

Analyte Order No. Analyte Order No.

Anti-TPO RA 1012-####-# FT3 RD 1016-10001

Anti-TG RA 1013-10001-# FT4 RD 1017-10001

TRAb RA 1015-10001 TSH RD 1018-10001

Thyrotropin RD 1013-10001 Calcitonin RD 1019-10001

RIA for thyroid diagnostics.

Microplate ELISA: Anti-Thyroglobulin, Anti-Thyroid Peroxidase,Anti-TSH receptor

• Monospecific determination of antibodies against thyroglobulin (TG), thyroidperoxidase (TPO), and thyrotropin receptor (TSH-R).

• Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis.

• Serum dilution 1 : 200 (exception: anti-TSH-R undiluted); conjugate class anti-human IgG, POD-labelled (anti-TSH-R: avidin-labelled).

• 3-point calibration (exception: anti-TSH-R, 5-point calibration).

• The quantification is carried out according to international referencepreparations (anti-TG: NIBSC 65/93; anti-TPO: NIBSC 66/387; anti-TSH-R:NIBSC 90/672).

• Thyroglobulin/TSH-R: native antigen; thyroid peroxidase: recombinant antigen.

Antigen Order No.

Thyroid peroxidase EA 1012-9601 G

Thyroglobulin EA 1013-9601 G

TSH receptor EA 1015-9601 G

TSH receptor (Fast-ELISA) EA 1015-9601-1 G

Incubated ELISA Anti-Thyroid antigens.


Order No. (Anti-TPO) FormatsRA 1012-####-# page 89

Order No. (Anti-TPO) FormatsEA 1012-9601 G page 86


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iesIndirect Immunofluorescence test: Dermatology Mosaic 9

• Screening and differentiation test for detection of skin-specific antibodies.

• Indication: autoimmune bullous dermatoses.


• The BIOCHIP Mosaic consists of 6 substrates:primate oesophagus,desmoglein 1-expressing cells, desmoglein 3-expressing cells, BP230-expressing cells (wholelength), BP230-expressing cells (gC) and BP180 (EUROPLUS). Thus acomprehensive antigen spectrum is available in a single analysis, allowingtargeted serological diagnosis.

• Autoantibodies against intercellular target structures (prickle cell desmosomes)can be reliably detected using tissue sections of oesophagus and tongue,although with this combination it is difficult to distinguish between desmoglein 1and desmoglein 3. When specific transfected cells are employed in addition, atargeted diagnosis in a single test run is possible.

• Antibodies against prickle cell desmosomes Antibodies against prickle celldesmosomes react with surface antigens of keratinocytes. Tissue sections ofoesophagus and tongue show a granular fluorescence in the intercellular matterin the whole stratum spinosum.

• When autoantibodies against BP180 or BP230 are present, the epidermalbasement membrane in the oesophagus or tongue is visible as a fine linearcolouring between the stratum basale and the connective tissue. Theseantibodies can be differentiated by means of BP180-NC16A-4X coated BIOCHIPSand cells transfected with BP230 (whole length or globular C-terminal domain(gC), respectively.

• This BIOCHIP Mosaic can be customised with further substrates if required, e.g.tongue (antibodies against prickle cell desmosomes, epidermal basementmembrane), bladder (antibodies against plakins), salt split skin (antibodiesagainst epidermal basement membrane).

Substrate Order No.

Desmoglein 1 (transfected / non-transfected cells) FA 1495-####-50

Desmoglein 3 (transfected / non-transfected cells) FA 1496-####-50

Oesophagus FA 1501-####

Oesophagus / Tongue FA 1501-####-1

Tongue FA 1502-####

Bladder mucosa FA 1507-####

Salt split skin FA 150b-####

Microplate ELISA: Anti-Desmoglein 1, Anti-Desmoglein 3, Anti-BP180-NC16A-4X, Anti-BP230-CF

• Monospecific detection of antibodies against desmoglein 1, desmoglein 3, BP180und BP230.

• Indication: autoimmune bullous dermatoses.



• Identical incubation conditions and times: all tests can be combined on onemicroplate.

• Recombinant antigens: extracellular domain of desmoglein 1 or 3, tetramer ofNC16A domain of BP180 protein, C-terminal segment of BP230 protein. Thecorresponding human cDNA is produced in E. coli (BP180-NC16A-4X, BP230-CF)or in mammalian cells (desmoglein 1, desmoglein 3).

Oesophagus: ab against epid. basal membrane(top left). Desmoglein 1 + 3 (middle left, bottomleft). BP230 gC (top right). BP230 whole length(middle right). BP180 (NC16A-4X) (bottom right).

Order No. FormatsFA 1501-####-9 G page 125

Order No. (Anti-Dsg-1) FormatsEA 1495-4801 G page 87

Incubated ELISA Anti-Desmoglein 1 and 3, Anti-BP180-NC16A-4X, Anti-BP230-CF

Autoantibodies against Antigens of the Skin


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CV2.1*

Ri

Yo

Hu

PNMA2 (Ma2/Ta)

Autoantibodies against Neuronal Antigens

Indirect Immunofluorescence Test: BIOCHIP Mosaic™ Cerebellum/Peripheral Nerves/Intestinal Tissue

• Screening test for the detection of antibodies against neuronal antigens.

• Indications: neurological diseases.

• Initial dilution 1 : 10; conjugate class anti-human IgAGM, FITC-labelled.

• Primate cerebellum and primate nerves are the standard substrates for thedetermination of various neuronal antibodies. The parallel use of primateintestine permits the reliable differentiation from other autoantibodies (e.g. ANA)and makes it possible to distinguish between anti-Ri and anti-Hu.

• Antibodies against grey matter react intensively with the stratum granulosumand in a weaker form with the stratum moleculare of the cerebellum. Targetantigen: glutamic acid decarboxylase (GAD). Clinical significance: stiff personsyndrome, diabetes mellitus type I.

• Antibodies against Yo stain exclusively the cytoplasm of the Purkinje cells in thecerebellum. Clinical significance: paraneoplastic neurological syndromes (PNS),indication of a malignoma.

• In the case of antibodies against Hu and Ri all neurone nuclei in the grey mattershow a granular fluorescence. Hu antibodies react in the intestine with cellnuclei of the plexus myentericus, whereas Ri antibodies do not. Clinicalsignificance: paraneoplastic neurological syndromes (PNS), indication of amalignoma.

• The white matter of the cerebellum is stained by antibodies against myelin,which present as hyaline cylinders in tissue sections of peripheral nerves. A“droplike“ ring-shaped fluorescence is observed in cross sections of nerves.

• The fluorescence of the Virchow-Robin space (cerebellum, optic nerve) and thepia is caused by autoantibodies developed in neuromyelitis optica (NMO-IgG).

• Antibodies against myelin-associated glycoprotein (MAG), on the other hand,show a streaky fluorescence pattern on nerve tissue and a mostly fine-granularring-shaped fluorescence on cross sections of peripheral nerves. Clinicalsignificance: paraproteinaemic neuropathy.

• The BIOCHIP Mosaic™ can be supplemented as required with further substrates,e.g. cerebrum (antibodies against astrocytes), optic nerve, primate liver plusHEp-2 cells (to rule out ANA), Crithidia luciliae (anti-dsDNA), primate stomach(parietal cell antibodies), Borrelia (neuroborreliosis-associated). Aquaporin-4(AQP4) transfected HEK cells allow a monospecific antibody determination insuspected cases of neuromyelitis optica (NMO).

Cerebellum: antibodies against GAD and Yo (top),against Hu and Ri (middle). Peripheral nerves:antibodies against myelin and MAG (bottom).

EUROLINE: Neuronal Antigens Profile 2

• Differentiation of antibodies against neuronal antigens.

• Indication: paraneoplastic neurologic syndromes (PNS).


• With the EUROLINE Neuronal Antigens Profile 2, six autoantibodies can bedetermined: antibodies against amphiphysin, CV2.1*, PNMA2 (Ma2/Ta), Ri, Yoand Hu.


• Additionally, EUROIMMUN offers a Westernblot for the detection of antibodiesagainst neuronal antigens: DW 1111-1601 G.

*) CV2 partial protein, which only contains the N-terminally localised epitopes of the antigen.

Incubated EUROLINE Neuronal Antigens Profile 2.



amphiphysin

control


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Yo RiRi

Hu

Indirect Immunofluorecence test: BIOCHIP Mosaic™ Hippocampus/Cerebellum/NMDA Receptor

• Screening test for detection of antibodies against glutamate receptors (typeNMDA, anti-N-methyl-D-aspartate receptor) und neuropil.

• Indication: NMDAR encephalitis.


• Immunohistochemistry with tissue sections of rat hippocampus and ratcerebellum allows identification of antibodies against glutamate receptors (typeNMDA) and other antibodies (e.g. VGKC and AMPA receptors). The parallel useof recombinant HEK293 cells enables sensitive and monospecific detection ofanti-glutamate receptor (type NMDA) antibodies and their differentiation fromother neuropil antibodies in a simple and efficient analysis.

• Antibodies against glutamate receptors (type NMDA) stain the neuropil of themolecular layer of the hippocampus as well as the granular layer of thecerebellum. They show a flat, smooth to fine-granular fluorescence in thecytoplasm of the transfected HEK293 cells. Clinical significance: Anti-NMDAreceptor encephalitis.

• If the monospecific detection of antibodies against glutamate receptors of typeNMDA is negative, neuropil fluorescence can indicate the presence of otherantibodies associated with limbic encephalitis (e.g. anti-VGKC antibodies, anti-AMPA receptor antibodies).

Antibodies against glutamate receptor (typeNMDA): rat hippocampus (top left), ratcerebellum (bottom left), untransfected cells (topright), transfected cells (bottom right).

EUROLINE-WB: Anti-Neuronal Antigens

• Determination of human autoantibodies against neuronal antigens.

• Indication: paraneoplastic neurological syndromes (PNS).


• EUROLINE-WB is a combination of westernblot and line blot techniques.Proteins of a primate cerebellum extract are electrophoretically separatedaccording to molecular mass and transferred onto a nitrocellulose membrane(westernblot). A membrane chip coated with highly purified recombinant Hu,recombinant Ri and recombinant Yo is subsequently applied to the westernblotstrip.

• Test strips can be automatically incubated using the system EUROBlotMaster(Seite 27).

Order No. FormatsDW 1111-####-2 G page 83

rec. Yo

Control

rec. Rirec. Hu

Incubated Anti-Neuronal Antigens EUROLINE-WB.

Order No. FormatsFA 111m-####-3 G page 118

Autoantibodies against Neuronal Antigens


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Autoantibodies against Islet Cell Antigens

Indirect Immunofluorescence Test: Primate Pancreas

• Detection of antibodies against islet cells.

• Indications: Differentiation between a late manifestation of diabetes type 1(latent autoimmune diabetes in adulthood, LADA) and diabetes type 2.

• For a reliable determination of antibodies against islet cells an extendedincubation time of 18 hours for the patient serum must be observed. Theincubation time may be reduced to 2 hours but this will lead to a decrease in thesensitivity of the antibody detection test.

• Standardised control with JDF units available (order no. CA 1021-0101-1).

• With indirect immunofluorescence autoantibodies against pancreas islets (ICA)can be detected in 80% of patients with new-onset diabetes type 1. Two targetantigens of ICA have been identified so far: the enzymes glutamic aciddecarboxylase (GAD) and tyrosine phosphatase (IA2).

• This BIOCHIP may be supplemented with further substrates, e. g. primatecerebellum for the detection of antibodies against GAD.

• The microscopic evaluation can be significantly simplified by using smallBIOCHIPs (1 x 1 mm). The BIOCHIPs appear almost completely in the field ofview and facilitate finding the islet cells, thus rendering a time-consumingsearch unnecessary, especially in negative samples.

Primate pancreas: antibodies against islet cells.

Microplate ELISA: Anti-GAD, Anti-IA2, Anti-GAD/IA2 Pool

• Monospecific detection of antibodies against glutamic acid decarboxylase(GAD), tyrosine phosphatase (IA2) or bispecific detection of both antibodies in asingle reagent well.

• Indications: early diagnosis of diabetes mellitus type 1, risk prediction in firstgrade relatives, prognosis of the clinical progression of diabetes type 1 forprediction of insulin dependence, differential diagnosis in gestational diabetes,differentiation between a late manifestation of diabetes type 1 (latentautoimmune diabetes in adulthood, LADA) and diabetes type 2.

• Use of undiluted samples. Similar incubation conditions and times. Manual orautomated test performance.

• Multipoint calibration. The quantitation is based on an international referencepreparation (NIBSC 97/550).

• GAD and IA2: human, recombinant antigens.

Antigen Order no.

Glutamic acid decarboxylase (GAD)EA 1022-9601 G

Tyrosine phosphatase (IA2) EA 1023-9601 G

GAD/IA2 Pool EA 1022-9601-1 G

Incubated ELISA anti-GAD.

RIA: Anti-GAD, Anti-IA2, Anti-Insulin

• Monospecific detection of antibodies against glutamic acid decarboxylase(GAD), tyrosine phosphatase (IA2) and insulin.

• Indications: Early diagnosis of diabetes mellitus type 1, risk prediction in firstgrade relatives, prognosis of the clinical progression of diabetes type 1 forprediction of insulin dependence, differential diagnosis in gestational diabetes,differentiation between a late manifestation of diabetes type 1 (latentautoimmune diabetes in adulthood, LADA) and diabetes type 2.

• Use of undiluted samples. Similar incubation conditions and times. Manual orautomated test performance.

• Test kit formats for 50 or 100 determinations.

• GAD and IA2: human, recombinant, 125I-labelled antigens, insulin: human,synthetic, 125I-labelled antigen.

Antigen Order no.

Glutamat-Decarboxylase (GAD) RA 1022-####

Tyrosin-Phosphatase (IA2) RA 1023-####

Insulin RA 1024-####

RIA Anti-IA2.

Order No. FormatsFA 1020-#### page 116

Order No. (Anti-GAD) FormatsEA 1022-9601 G page 86

Order No. (Anti-IA2) FormatsRA 1023-#### page 89


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iesIndirect Immunfluorescence Test: Primate Stomach with Urea

Pretreatment

• Screening test for detection of antibodies against parietal cells.

• Indications: forms of chronic atrophic gastritis, pernicious anemia, funicularmyelosis, various autoimmune endocrinopathies such as Basedow’s andAddison’s diseases.


• Primate stomach is the standard substrate for detection of parietal cellantibodies. For titration, stomach tissue from rat or mouse is sufficient.

• With positive results the parietal cells show a course granular to clumpyfluorescence, and the surrounding areas are usually dark.

• Parietal cell antibodies (PCA) are often mixed up with antibodies againstmitochondria (AMA) in microscopic analysis. The latter give an even finegranular fluorescence of the parietal cell cytoplasm, with the surrounding regionshowing a (weaker) reaction.

• For reliable differentiation of both types of antibody, a 30-minute pretreatmentof the tissue sections with urea-glycine buffer (order no. ZF 1140-0101, see page151) is recommended.

• The cytomplasmic fluorescence of parietal cells resulting from PCA occurs withthe same intensity with or without urea pretreatment. The typical pattern ofmitochondrial antibodies is almost completely supressed by urea pretreatment,greatly facilitating PCA diagnostics.

• In some AMA-positive samples it is possible to detect PCA that are obscured bythe AMA pattern in conventional tissue sections.

• The urea-pretreated tissue shows a significantly darker background, enablingspecific fluorescence to be more easily and reliable identified.

• This BIOCHIP can be supplemented with additional substrates, for example,thyroid (thyroid peroxidase, thyroglobulin), pancreas (pancreas islets), adrenalgland (adrenal cortex), ovary (ovary antigens), testis (Leydig cells), and intrinsicfactor.

Primate stomach: antibodies against parietalcells. With urea-pretreatment (top) and withouturea-pretreatment (bottom).

Microplate ELISA: Anti-Parietal Cells

• Monospecific detection of antibodies against parietal cells (PCA).

• Indications: forms of chronic atrophic gastritis, pernicious anemia, funicularmyelosis, various autoimmune endocrinopathies such as Basedow’s andAddison’s diseases



• Native antigen: H+/K+-ATPase, purified by affinity chromatography.

Incubated ELISA Anti-Parietal Cells.

Order No. FormatsFA 1360-#### G page 122


Primate stomach: antibodies against mitochon-dria. With urea-pretreatment (top) and withouturea-pretreatment (bottom).

Autoantibodies against Parietal Cells (PCA)


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Autoantibodies against Granulocyte Cytoplasm (cANCA/pANCA)

Indirect Immunofluorescence Test: EUROPLUS™ GranulocyteMosaic 23

• Screening test for the detection of antibodies against granulocyte cytoplasm(ANCA).

• Indications: Wegener’s granulomatosis, various forms of glomerulonephritis,primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease.

• Initial dilution: serum 1 : 10; conjugate anti-human IgG, FITC-labelled.

• Using ethanol-fixed granulocytes, antibodies against granulocyte cytoplasm canbe detected. In this case, two fluorescence patterns have to be differentiated: agranular fluorescence which is distributed evenly over the entire cytoplasm,leaving the cell nuclei free (cytoplasmic type, cANCA) or a smooth fluorescencewrapped ribbon-like around the cell nuclei (perinuclear type, pANCA).

• Antibodies against all relevant granulocyte antigens as well as against further,as yet unknown antigens are detected simultaneously:

Pattern Target antigen Associated diseases

cANCA Proteinase 3 Wegener’s granulomatosis

pANCA Myeloperoxidase Microscopic arteritis, Churg-Strauss syndrome,polyarteritis nodosa

pANCA Elastase Ulcerative colitis, Crohn’s disease, primary sclero-sing cholangitis, systemic lupus erythematosus

pANCA Cathepsin G Ulcerative colitis, primary sclerosing cholangitis,Crohn’s disease

pANCA Lysozyme Ulcerative colitis, primary sclerosing cholangitis,Crohn’s disease

pANCA Lactoferrin Ulcerative colitis, primary sclerosing cholangitis,Crohn’s disease, systemic lupus erythematosus,rheumatoid arthritis

cANCA BPI Primary sclerosing cholangitis, ulcerative colitis,or pANCA Crohn’s disease

pANCA unknown Ulcerative colitis, Crohn’s disease

• The primate liver enables one to differentiate between pANCA and anti-nuclearantibodies (ANA) which can easily be confused when using ethanol-fixed granu-locytes: In the case of a positive ANA result all nuclei of the hepatocytesfluoresce, whereas in the case of pANCA (as well as cANCA) only thegranulocytes in the sinusoids of primate liver fluoresce.

• The EUROPLUS substrates PR3 and MPO as monospecific tests can confirmresults from conventional granulocyte screening tests. Recombinant GBMEUROPLUS substrate also provides additional reliability for diagnosis. Whenfluorescence patters are unclear (e.g. unspecific fluorescence caused by othercytoplasmic antibodies) these substrates facilitate evaluation.

Microplate ELISA: ANCA Profile

• Differentiation of antibodies against granulocyte cytoplasm (ANCA).

• Indications: Wegener’s granulomatosis, various forms of glomerulonephritis,primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease.


• 6 relevant anti-granulocyte antibodies can be detected simultaneously andmonospecifically: autoantibodies against proteinase 3, lactoferrin, myelo-peroxidase, elastase, cathepsin G, BPI.

• 1-point calibration, semi-quantitative. Calibrator pool and serum sample on thesame microplate strip.

• Native antigens, purified by affinity chromatography.

• Available individual ELISA (3-point calibration, quantitative):

Antigen Order No.

Proteinase 3 (Capture ELISA) EA 1201-9601-1 G

Proteinase 3 (PR3-hn-hr: native/recombinant) EA 1201-9601-2 G

Myeloperoxidase EA 1211-9601 G

Incubated ELISA ANCA Profile (antigens: pro-teinase 3, lactoferrin, myeloperoxidase, elastase,cathepsin G, BPI.



EUROPLUS™ Granulocyte Mosaic 23 (granuloc.(EOH), granuloc. (HCHO), PR3, MPO, HEp-2, pri-mate liver): pattern pANCA, formalin-resistant.


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Screening test indirect immunofluorescence: BIOCHIP sextet granulocytes (EOH), granulocytes (HCHO),

EUROPLUSTM microdots PR3, EUROPLUSTM microdots MPO, human epithelial cells (HEp-2), and primate liver

AAb againstPR3-hn-hr

WG 80-90 %

AAb againstBPI

WG 5 %

ELISA: anti-PR3-hn-hr / ANCA Profile (BPI)

cANCA

Cytoplasmic fluorescenceof granulocytes (A, B, F)

WG 80-90 %MPA 10-15 %CSS 10-20 %PAN < 9 %

pANCA

Perinuclear fluorescence of granulocytes (A, F)

MPA 42-70 %CSS 18-60 %SLE 9-25 %RA 3-25 %

pANCA, formalin-resistant

At B cytoplasmicfluorescence

pANCA, formalin-sensitive

At B no cytoplasmicfluorescence

only ANA

Fluorescence of all cell nuclei(A, E, F)

pANCA, formalin-res. & ANA

Cytoplasmic fluorescenceof granulocytes (B)

pANCA, formalin-sens. & ANA

Nuclei of granuloc. brighter thannuclei of hepatocytes (F), B neg.

pANCA, formalin-sens.? & ANA

ANCA reaction at A,ANA reaction at E & F

Qualified ANA diagnostics: screening test usingHEp-2 cells/primate liver (E, F), differentiationusing ELISA, EUROASSAY, EUROLINE, Westernblot

See EUROIMMUN poster: "Strategy for Determinationof Autoantibodies against Cell Nuclei (ANA)

and Cytoplasm Components"

AAb againstMPO

ELISA: anti-MPO

AAb against PR3, MPO,elastase, cathepsin G,

BPI, lactoferrin

WG 5 % (BPI)MPA 53 % (MPO)MPA 3 % (LF)RA, vasculitides 45 % (LF)SLE 6 % (EL)

ELISA: ANCA Profile

ANA and pANCA

Fluorescence of all cell nuclei(A, E, F), granuloc. accent. (F)

MPA 42-70 %

CU 67 %MC 7 %PSC 87 %

MPA 53 %

F

Primateliver

E

HEp-2cells

B

Granulocytes(HCHO-fixed)

D

EUROPLUSTM

MPOmicrodots

C

EUROPLUSTM

PR3microdots

A

Granulocytes(EOH-fixed)

AAb against dsDNA, ssDNA, nucleosomes, histones, nuclear membrane, nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Ku, cyclin I (PCNA), mitosin (CENP-F, cyclin II), nuclear dots, centromeres (CENP B), spindle fibres, midbody, centrioles, Scl-70, PM-Scl, fibrillarin, RNA polymerase I, NOR, ribosomal P-proteins, Jo-1, PL-7, PL-12, Mi-2, mitochondria (AMA), lysosomes, Golgi apparatus, vimentin, tropomyosin, actin.

Cost-effective Strategy for the Detection ofAutoantibodies against Granulocyte Cytoplasm (ANCA)

ANA: anti-nuclear antibodies BPI: bactericidal permeability increasing protein cANCA: anti-neutrophil cytoplasmic antibodies, cytoplasmic type CD: Crohn‘s disease CSS: Churg-Strauss syndrome EL: elasta-se EOH: ethanol HCHO: formalin HEp-2: human epithelial cells IFT: immunofluorescence test LF: lactoferrin MPA: microscopic polyangiitis MPO: myeloperoxidase PAN: polyarteritis nodosa pANCA: anti-neutro-phil cytoplasmic antibodies, perinuclear type PR3: proteinase 3 PSC: primary sclerosing cholangitis RA: rheumatoid arthritis SLE: systemic lupus erythematosus UC: ulcerative colitis WG: Wegener‘s granulomatosis

The highest diagnostic sensitivity in the determination of autoantibodies against neutrophil granulocytes (ANCA) is achieved by using indirect immunofluorescence

and assays with defined target antigens (particularly PR3 and MPO) simultaneously at the start. However, under the pressure of cost optimisation, an immunofluo-rescence test may be performed on its own and then followed up by specific ELISA tests only if the result is positive. Ethanol-fixed human granulocytes are the standard substrate for indirect immunofluorescence. With this substrate two relevant fluorescence patterns can be differentiated: the cytoplasmic type (cANCA) associated with Wegener’s granulomatosis and the perinuclear type (pANCA), which indicates a range of various diseases. The differentiation of pANCA from antibodies against cell nuclei (ANA) is often difficult. Therefore, HEp-2 cells (possibly with sedimented granulocytes) or primate liver are used as an additional substrate. If ANA and pANCA occur together, the granulocytes show a much brighter fluorescence than the cell nuclei. Thanks to EUROIMMUN BIOCHIPs it is not necessary to incubate human epithelial cells on a second slide in parallel for the exclusion of cell nucleus antibodies, since all substrates are present in one and the same test field. A fourth BIOCHIP with formalin-fixed human granulocytes detects a large proportion of the diagnostically relevant antibodies against myeloperoxidase, whereas other pANCA (which are particularly important in gastroenterology) and almost all antibodies against cell nuclei (whose differentiation is a separate chapter in autoantibody diagnostics) are generally completely suppressed. The EUROPLUSTM substrates PR3 and MPO help to confirm diagnosis and allow a quick and reliable interpretation of results even in problematic cases.


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Antibodies against Endomysium and Gliadin

Indirect Immunofluorescence Test: EUROPLUS™ Primate Liverand Gliadin (GAF-3X) BIOCHIPs

• Detection of antibodies against endomysium and gliadin.

• Indications: gluten-sensitive enteropathy (celiac disease, non-tropical sprue),Duhring’s herpetiform dermatitis.

• Initial dilution 1 : 10; conjugate class anti-human IgA or IgG, FITC-labelled.

• Autoantibodies against endomysium react with many types of tissue, e.g.primate oesophagus. The most suitable substrate, however, is primate liver: inthe case of a positive sample, filamentous linings of the intralobular sinusoidsreact.

• With the gliadin (GAF-3X)-coated BIOCHIP, antibodies against gliadin can beanalyzed in one and the same test procedure.

• Both anti-endomysium antibodies and antibodies against gliadin (class IgA) arereliable serological markers for an active gluten-sensitive enteropathy.Therefore, their determination can in many cases replace endoscopy and biopsy.

Primate liver and gliadin (GAF-3X) BIOCHIP: anti-bodies against endomysium and gliadin.

Microplate ELISA: Anti-Gliadin (GAF-3X)

• Monospecific detection of antibodies against gliadin.


• Serum dilution 1 : 200; conjugate class anti-human IgA or IgG, POD-labelled.

• 3-point calibration. Identical incubation conditions and times: the investigationof IgA and IgG antibodies can be combined without difficulty on one and thesame microplate.

• Antigen: Gliadin-analogue fusion peptide (GAF-3X).

• The quantitative determination of antibodies against gliadin is very suitable formonitoring the progress of the disease, compliance with a gluten-free diet, or agluten tolerance test.

Incubated ELISA Anti-Gliadin (GAF-3X).

Incubated ELISA Anti-Tissue Transglutaminase(Endomysium).

Microplate ELISA: Anti-Tissue Transglutaminase (Endomysium)

• Monospecific detection of antibodies against tissue transglutaminase.


• Serum dilution 1 : 200; conjugate class anti-human IgA or IgG, POD-labelled.


• Antigen: recombinant, expression with the baculovirus vector in insect cells.

Order No. FormatsFA 1914-####-1 A or G page 132

Order No. FormatsEV 3011-9601 A or G page 95

Order No. FormatsEA 1910-9601 A or G page 88


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EUROIMMUN PRODUCTS FOR INFECTIOUS SEROLOGY


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Antibodies against Borrelia

Indirect Immunofluorescence Test: EUROPLUS™ Anti-Borreliaafzelii, Borrelia burgdorferi, VlsE and OspC Antigen

• Sensitive screening test for the detection of anti-Borrelia antibodies.

• Indications: erythema chronicum migrans, lymphadenosis cutis benigna, lym-phocytic meningoradiculitis, carditis, arthritis, acrodermatitis chronica atro-phicans, neuroborreliosis.

• Initial dilution 1 : 10 (IgM), 1 : 100 (IgG).

• If antibodies against Borrelia afzelii or Borrelia burgdorferi are present, a distinctfluorescence of the bacteria in the smear is obtained.

• With the VlsE or OspC coated BIOCHIPs antibodies against the highly specificand highly sensitive marker antigens VlsE (IgG) or OspC (IgM) can bedetermined monospecifically in one and the same test procedure. If theseantigens fluoresce the antibody result is positive even if the bacteria smearsshow a negative reaction. Thus, the BIOCHIP Mosaic helps to increase specificityand sensitivity in Borrelia diagnostics.

• The BIOCHIP can be supplemented as required using further substrates, e.g.Borrelia burgdorferi sensu stricto (strains CH or USA) and TBE virus infectedcells.

Antibodies against Borrelia afzelii, VlsE (top),Borrelia burgdorferi and OspC (bottom).

Incubated ELISA Anti-Borrelia plus VlsE.

Microplate ELISA: Anti-Borrelia plus VlsE

• Sensitive screening test for the detection of anti-Borrelia antibodies.


• Serum dilution 1 : 100; conjugate class anti-IgG, anti-IgM or anti-IgAGM (VlsE: -IgG only), POD-labelled.

• 3-point calibration (IgG and IgM). Identical incubation conditions and times: alltests can be combined without difficulty on one and the same microplate.

• Antigens: extract of Borrelia burgdorferi sensu stricto, Borrelia garinii andBorrelia afzelii (whole antigen) / recombinant VlsE from Borrelia burgdorferisensu stricto. VlsE (variable major protein-like sequence, expressed) is a newlycharacterized surface protein of Borrelia which is expressed exclusively in vivoand which contains conserved and highly immunogenic epitopes.

• IgM test kit (Anti-Borrelia) includes IgG/RF absorbent in sample buffer for IgGabsorption in preparation for the determination of specific IgM class antibodies.

Microplate ELISA: Anti-Borrelia plus VlsE, Antibody Determinationin Serum and Cerebrospinal Fluid for Detection of IntrathecalSynthesis of Specific Antibodies against Borrelia

• Antibody determination in serum and cerebrospinal fluid (CSF).

• Indication: Neuroborreliosis.

• CSF dilution 1 : 2, serum dilution 1 : 404; conjugate class anti-IgG, POD-labelled.


• Microplate ELISA for the detection of Borrelia antibodies of class IgM in serumand CSF are also available.

Order No. FormatsFI 2136-####-1 G or M page 136

Order No. FormatsEI 2132-9601 G or M page 91

Order No. FormatsEI 2132-9601 L G page 91

Table-based evaluation of the CSQrel.


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p 83

p 31, Osp A

p 39, Bmp Ap 41, Flag.

p 25, Osp C

p 30

p 19p 17

p 21

VlsE

VlsE B. afzelii

VlsE B. gariniiVlsE B. burgdorferi

Lipid B. afzeliiLipid B. burgdorferip83 B. afzeliip41 B. gariniip39 B. garinii

OspC B. garinii

p58p21p20p19p18

IgG

VlsE B. burgd.p41 B. afzeliip39 B. afzeliiOspC B. afzelii

OspC B. gariniiOspC B. burgd.

IgM

Automated Evaluation of Incubated Membrane Strips with the System EUROLineScan

• The program EUROLineScan from EUROIMMUN has been developed to enable quantitative evaluation of membrane based test systems,facilitate management of data, and provide detailed documentation of results — tasks which have until now required considerable time.

• First, the incubated test strips are scanned using a flatbed scanner or camera system.

• EUROLineScan recognizes the position of the strips, even if they have been placed inexactly, identifies the bands, and measures theirintensity. The automated evaluation can be monitored, and it is possible to supplement the data manually.

• The results are then saved together with the image data. It is no longer necessary to archive (potentially infectious) incubated test strips.A separate results sheet can be produced for each patient.

Antibodies against Borrelia

Incubated Anti-Borrelia EUROLINE-RN-AT .

Order No. FormatsDN 2131-3201 G or M page 81

Control band

Anti-Borrelia EUROLINE-RN-AT

• Specific confirmatory test for the detection of antibodies against Borrelia.


• The Anti-Borrelia EUROLINE is coated with both native and recombinantproteins and provides a unique mixture of Borrelia specific antigens: Theclassical antigens OspC, p83 and p39, which show the highest specificity in theirnative form, were accurately cut from a Westernblot and applied onto themembrane of the line blot. Five new, recombinant designer antigens (p18, p19,p20, p21, p58) having a very high specificity (IgG) were identified usingbioinformatic analysis of the Borrelia genome. For the first time, lipids which

have been proven to be immunoreactive and were extracted from the Borreliamembranes, three native OspC antigens (IgM) from B. afzelii, B. burgdorferiand B. garinii and three different VlsE antigens (IgG) from B. afzelii, B.burgdorferi and B. garinii are available on the line blot.

• The serological hit rate is increased by 10% by using three OspC variants in theIgM test.

• Serum dilution 1 : 50; conjugate class anti-IgG or anti-IgM, AP-labelled.

Incubated EUROLINE-WB Anti-Borrelia.

Order No. FormatsDY 2131-1601-1 G or M page 84

Control band

EUROLINE-WB: Anti-Borrelia (Whole Antigen plus VlsE)

• Specific confirmatory test for the detection of antibodies against Borrelia.

• EUROLINE-WB is a combination of westernblot and line blot techniques. AnSDS extract of a Borrelia afzelii strain is electrophoretically separated accordingto molecular mass and transferred onto a nitrocellulose membrane. Amembrane chip coated with highly purified recombinant VlsE-Antigen is thenadded to the westernblot strips.

• By additionally determining antibodies against VlsE the serological hit rate canbe increased by 20% compared to whole extract Westernblots and by 30%compared to recombinant antigen Westernblots. Of all recombinant antigens,VlsE possesses the highest sensitivity for the detection of a Borrelia infection.Over 85% of IgG-positive sera could be identified at a glance by assessing theVlsE band. VlsE allows detection of antibodies against all Borrelia species, andthe risk of a false negative reaction due to species differences is ten times lower.


Control band


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Antibodies against Epstein-Barr Virus (EBV)

Microplate ELISA: Anti-EBV-CA, Anti-EBNA-1, Anti-EBV-EA

• Specific confirmatory test for antibodies against EBV-CA, EBNA-1 or EBV-EA.

• Indications: infectious mononucleosis, Burkitt’s lymphoma, nasopharyngealcarcinoma.

• Serum dilution 1 : 100; conjugate class anti-IgA, -IgG or IgM, POD-labelled.

• 1-point calibration, semi-quantitative (IgA, IgM) or 3-point calibration, quantita-tive (IgG). Identical incubation conditions and times: all tests can be combinedwithout difficulty on one and the same microplate.

• EBV-CA: native antigen, purified by affinity chromatography; EBNA-1 and EBV-EA:recombinant antigen.

• IgM test kit includes IgG/RF absorbent in sample buffer for IgG absorption inpreparation for the determination of specific IgM class antibodies.

• Available individual ELISA:

Antigen Order No.

EBV-CA EI 2791-9601 A, G or M

EBNA-1 EI 2793-9601 G

EBV-EA EI 2795-9601 A, G or M

Incubated ELISA Anti-EBNA-1.

Order No. FormatsFI 2799-####-21 X page 148

Order No. (anti-EBNA-1) FormatsEI 2793-9601 G page 95

Patient 1: EBV-CA (IgG) EBV-CA (IgG): urea-treated EBV-CA (IgM) EBV-EA (IgG) EBNA (IgG)

Patient 2: EBV-CA (IgG) EBV-CA (IgG): urea-treated EBV-CA (IgM) EBV-EA (IgG) EBNA (IgG)

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Indirect Immunofluorescence Test: BIOCHIP Sequence EBV

• Gold standard for the determination of antibodies against the EBV-CA antigens (Epstein-Barr virus capsid antigen), EBV-EA (Epstein-Barr early antigen) and EBNA (Epstein-Barr nuclear antigen).

• Indication: infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma (NPC).

• IgG antibodies against EBV-CA indicate an EBV infection. An at least twofold increase in titer and the absence of antibodies againstEBNA at the same time is characteristic for the early phase of the infection. IgM antibodies against EBV-CA and antibodies againstEBV-EA can also be found in acute infections, but they do not necessarily always occur. The presence of antibodies against EBNAgenerally indicates the late phase of an EBNA infection.

• In cases of an acute EBV infection which cannot be reliably discriminated from a relapse or reinfection, the determination of theantibody avidity using a modified immunofluorescence test as an additional parameter is useful. This requires an additional incubationwith urea solution (ZF 1130-0801). The determination of low-avidity antibodies against EBV-CA indicates an acute infection.

• For the monospecific confirmation of EBV-CA antibodies in the same test procedure the BIOCHIP containing ECV-CA is supplementedwith the antigen substrates gp125 antigen (native) and p19 antigen (recombinant) (EUROPLUS FI 2791-####-20 G or M).

• For highly differentiated diagnostics the BIOCHIP Sequence EBV (FI 2799-####-1 X) can be supplemented by using the antigens gp125and p19 (EUROPLUS FI 2799-####-21 X).

• Due to the high prevalence of anti-EBV-CA IgA in NPC patients, the parameter is well suited for screening. Confirmation of the resultby determination of IgA antibodies against EBV-EA is recommended. Further anti-EBV test kits for indirect immunofluorescence:

Substrate Order No. Substrate Order No.

EBV-CA FI 2791-#### A, G or M EBV-EA FI 2795-#### A or G

EBNA FI 2793-#### G EBV-CA & EBV-EA FI 2791-####-2 A or G


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0

2

4

6

8

10

0 25 50 75 100

VCA gp125VCA p19EBNA-1

p22EA-D

VCA 125

VCA 65

VCA 40/41/42

VCA 33

VCA 22

EA REBNA-1

EA D

Antibodies against Epstein-Barr Virus (EBV)

EUROLINE: EBV Profile 2

• Differentiation of antibodies against Epstein-Barr virus antigens.


• Serum dilution 1 : 100; conjugate class anti-human IgG or IgM, AP-labelled.

• With the EUROLINE EBV Profile 2, five different antibodies can be determined:antibodies against VCA gp125, VCA p19, EBNA-1, p22, EA-D.

• Recombinant antigens (exception: VCA gp125, native, purified by affinity chro-matography).

• EBNA-1 (IgG) negative und VCA (IgG and IgM) positive: acute (fresh) infection.

• EBNA-1 (IgG) and VCA (IgG) positive and VCA (IgM) negative: late phase ofinfection.

• EBNA-1 (IgG) negative, but band p22 (IgG) and VCA (IgG) positive: late phase ofinfection with loss of anti-EBNA-1.


Westernblot: Anti-EBV

• Specific confirmatory test for the detection of antibodies against Epstein-Barrvirus antigens, differentiation of antibodies against Epstein-Barr virus antigens.



• Antigens: whole antigen, SDS extract.

• Bands from all specific antigens are included and clearly separated.

• EBNA-1 (IgG) negative und VCA (IgG and IgM) positive: acute (fresh) infection.

• EBNA-1 (IgG) and VCA (IgG) positive and VCA (IgM) negative: late phase ofinfection.

• EBNA-1 (IgG) negative, but band p22 (IgG) and VCA (IgG) positive: late phase ofinfection with loss of anti-EBNA-1.

• Test strips can be automatically incubated and evaluated using the systemsEUROBlotMaster und EUROLineScan (see page 27). Incubated Westernblot Anti-EBV.

Order No. FormatsDN 2790-1601-2 G or M page 81

Order No. FormatsDY 2790-1501 G or M page 85

Control band

Avidity of antibodies against EBV-CA (IgG)

Relative Avidity Index (RAI) in %

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RAI =E

with urea

Ewithout urea

Primary Infection

Previous Infection

Determination of Low-Avidity Antibodies against EBV-CA

• An alternative principle for the serological diagnosis of fresh infections with EBVhas been established by investigating the antibody avidity.


• To identify low-avidity antibodies against EBV-CA in a patient’s serum, twomicroplate ELISA or immunofluorescence tests are performed in parallel: onetest is carried out in the conventional way, the other one includes urea treatmentbetween incubations with patient’s serum and peroxidase-labelled anti-humanIgG, resulting in the detachment of low-avidity antibodies from the antigens.

• Low-avidity antibodies against EBV-CA are present if the ELISA extinction issignificantly reduced by urea treatment. For an objective interpretation, therelative avidity index (RAI) can be calculated out of the measured values withand without urea incubation.

• With the immunofluorescence test the presence of low-avidity antibodies hasbeen proved if the test using urea treatment gives a far weaker fluorescencethan the two-step test.

Control

Incubated EUROLINE EBV Profile 2.

Order No. (IIFT)FI 2791-#### XOrder No. (ELISA) FormatsEI 2791-####-1 G page 95 and 147


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p 120, CagA

p 33

p 95, VacA

p 30p 29, UreAp 26

p 19, OMPp 17

p 66, UreB

Antibodies against Helicobacter pylori

Indirect Immunofluorescence Test: Anti-Helicobacter pylori

• Sensitive screening test for the detection of antibodies against Helicobacterpylori.

• Indications: gastritis, ulcus ventriculi et duodeni. Late consequences: MALTlymphomas and adenocarcinomas.

• Initial dilution 1 : 10 (IgM), 1 : 100 (IgG), 1 : 32 (IgA).

• If antibodies against Helicobacter pylori are present, a distinct fluorescence ofthe bacteria in the smear is obtained.

• A positive IgA result correlates well with the activity of a gastritis. An increasedIgG antibody titer is considered to be a marker for chronic infections. A signifi-cant drop in the IgG antibody titer about 6 months after therapy is a sign ofsuccess.

• The BIOCHIP can be supplemented as required with further substrates, e.g. otherinfectious agents or tissue sections of primate stomach.

Antibodies against Helicobacter pylori.

Microplate ELISA: Anti-Helicobacter pylori

• Sensitive screening test for the detection of antibodies against Helicobacterpylori.


• Serum dilution 1 : 100; conjugate class anti-IgA or anti-IgG, POD-labelled.

• Antibodies against Helicobacter pylori antigens can be determined quantitativelyin RU/ml.

• 1-point calibration, semi-quantitative (IgA) or 3-point calibration, quantitative(IgG). Identical incubation conditions and times: both tests can be combinedwithout difficulty on one and the same microplate.

• Native antigens.Incubated ELISA Anti-Helicobacter pylori.

EUROLINE-WB: Anti-Helicobacter pylori

• Specific confirmatory test for the detection of antibodies against Helicobacterpylori.


• Serum dilution 1 : 50; conjugate class anti-IgA or anti-IgG, AP-labelled.

• EUROLINE-WB is a combination of westernblot and line blot techniques. AnSDS extract of a Helicobacter pylori strain is electrophoretically separatedaccording to molecular mass and transferred onto a nitrocellulose membrane(westernblot). Two membrane chips coated with highly purified recombinantCagA and VacA are subsequently applied to the westernblot strips.



Incubated EUROLINE-WB Anti-Helicobacter pylori.

Order No. FormatsFI 2080-#### A or G page 134

Order No. FormatsEI 2080-9601 A or G page 91

Order No. FormatsDY 2080-1601-1 A or G page 84

Control band

Alignment bar


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gG 1

gC 1

gG 2

Antibodies against Herpes Simplex Virus (HSV)

Indirect Immunofluorescence Test: BIOCHIP Mosaic™ HSV-1/HSV-2

• Sensitive screening test for the detection of antibodies against herpes simplexviruses.

• Indication: herpes simplex.

• Initial dilution 1 : 10 (IgM), 1 : 100 (IgG).

• If antibodies against herpes simplex-2 virus are present in the sample, a typicalfluorescence of the infected cells is obtained – mainly in the outspread cyto-plasm, less in the cell nuclei.

• As HSV-1 and HSV-2 are morphologically and immunologically closely related,cross-reactions can occur. Differentiation may be attempted by testing a serumagainst both antigen substrates and comparing the titers.

• The BIOCHIP Mosaic™ can be supplemented as required with further substrates,e.g. other infectious agents.

• Anti-HSV individual tests for indirect immunofluorescence:

Substrate Order No.

HSV-1 FI 2531-#### G or M

HSV-2 FI 2532-#### G or M

HSV-1 and -2 FI 2531-####-1 G or M

Antibodies against HSV-1 and HSV-2.

Microplate ELISA: Anti-HSV-1, Anti-HSV-2

• Specific confirmatory tests for antibodies against HSV-1 or HSV-2.


• Serum dilution 1 : 100; conjugate class anti-IgG or anti-IgM, POD-labelled.

• 1-point calibration, semiquantitative (IgM) or 3-point calibration, quantitative(IgG). Identical incubation conditions and times: all tests can be combinedwithout difficulty on one and the same microplate.

• Antigens: type-specific glycoproteins C1 or G2, purified by affinity chromato-graphy. Cross-reactions do not occur.


• Available individual ELISA:

Antigen Order No.

HSV-1 EI 2531-9601-2 G or M

HSV-2 EI 2532-9601-2 G or M

HSV-1/2-Pool EI 2531-9601-1 G or M

Incubated ELISA Anti-HSV-1.

EUROLINE-WB: Anti-HSV

• Specific confirmatory test for the differentiation of antibodies against HSV-1 andHSV-2.



• EUROLINE-WB is a combination of westernblot and line blot techniques.Proteins from an SDS extract of HSV-1 are electrophoretically separatedaccording to molecular mass and transferred onto a nitrocellulose membrane. Amembrane chip coated with HSV-2 type-specific glycoprotein G2 (gG 2), purifiedby affinity chromatography, is then added to the westernblot strips.


• The gG 2 band allows the simple differentiation between HSV-1 and HSV-2infections.


Incubated EUROLINE-WB Anti-HSV.

Order No. FormatsFI 2531-####-1 G or M page 141

Order No. (anti-HSV-1) FormatsEI 2531-9601-2 G or M page 93

Order No. FormatsDY 2531-1601-1 G or M page 85

Alignment bar

Control band


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Antibodies against Chlamydia

Indirect Immunofluorescence test: Anti-Chlamydia MIF (Micro-Immunofluorescence test)

• Serological gold standard for the determination of antibodies against Chlamydia.

• Indication: trachoma, urogenital infections, lymphogranuloma venereum, laryn-gitis, sinusitis, bronchitis, pneumonia, psittacosis.

• Initial dilution 1 : 10 (IgA), 1 : 100 (IgG), 1 : 10 (IgM).

• The micro-immunofluorescence test uses purified elementary bodies of thespecies C. trachomatis, C. pneumoniae and C. psittaci as the antigen. The mutuallipopolysaccharide (LPS) antigen is inactivated to minimise cross reactivity.

• The evaluation of the MIF could be significantly facilitated compared to con-ventional test systems by using a cell-based substrate.

• The fourth BIOCHIP with non-infected cells allows a reliable differentiationbetween unspecific and specific fluorescence.Anti-Chlamydia MIF.

Microplate ELISA: Anti-Chlamydia trachomatis

• Monospecific detection of antibodies against Chlamydia trachomatis.

• Indication: trachoma, conjunctivitis, urogenital infections, pneumonia in infants,lymphogranuloma venereum.

• Serum dilution 1 : 100, conjugate class anti-human IgA, IgG or IgM, POD-labelled.

• 1-point calibration, semiquantitative (IgA and IgM) or 3-point calibration, quanti-tative (IgG).

• Antigen: native MOMP antigen (major outer membrane protein). MOMP is atransmembrane protein and represents the main part of the outer membrane ofthe elementary bodies. Protein purification starts with BGM cells infected withChlamydia trachomatis of the serotype K.


Incubated ELISA Anti-Chlamydia trachomatis.

Incubated ELISA Anti-Chlamydia pneumoniae.

Microplate ELISA: Anti-Chlamydia pneumoniae

• Monospecific detection of antibodies against Chlamydia pneumoniae.

• Indication: laryngitis, sinusitis, bronchitis, pneumonia.

• Serum dilution 1: 100, conjugate class anti-human IgA, IgG or IgM, POD-labelled.

• 1-point calibration, semiquantitative (IgA and IgM) or 3-point calibration, quanti-tative (IgG).

• Antigen: cell lysate from HL cells, strain CDC/CWL-029.


Order No. FormatsFI 2191-####-3 A, G or M page 138

Order No. FormatsEI 2191-9601 A, G or M page 92

Order No. FormatsEI 2192-9601 A, G or M page 92


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Antibodies against Emerging Viruses

Indirect Immunofluorescence Test

• Over the past years it has been observed that a number of new viruses("emerging viruses") and other pathogens has spread worldwide, introducingsince then unknown diseases into previously unaffected regions.

• EUROIMMUN offers a broad spectrum of indirect immunofluorescence tests forthe detection of specific antibodies against:

• Many of these substrates are available as single substrate with non-infectedcells or as useful combinations (syndrome or geographically orientated) for theinvestigation of serum samples.

• IgG absorption as preparatory step for the determination of specific antibodiesof class IgM: page 60.

• Cross reactions within the virus family, especially with Flaviviruses, should betaken into consideration since they may cause false-positive results. The in-fectious agent can be determined by titration of the sample and comparison oftiters.

Antibodies against Plasmodium, Rift valley fevervirus, Chikungunya virus.

Microplate ELISA: Anti-TBE Virus, Anti-West Nile Virus,Anti-Dengue Virus

• Monospecific determination of antibodies against TBE, West Nile and Denguevirus.

• Serum dilution 1: 100, conjugate class anti-human IgG or IgM, POD-labelled.

• 1-point calibration, semiquantitative (IgM) or 3-point calibration, quantitative(IgG). Similar incubation conditions and times: All tests can be combined on oneand the same microplate.

• IgM test kit with IgG/RF absorbent in the sample buffer for IgG absorption aspreparatory step for the determination of specific IgM antibodies.

• Available single ELISA:

Antigen Order No.

TBE EI 2661-9601 G or M, avidity, Ab determination in CSF

TBE „Vienna“ EI 2661-9601-9 G

WNV EI 2662-9601 G or M, avidity

Dengue EI 266b-9601 G or M

Incubated ELISA Anti-TBE virus, Anti-WNV, Anti-Dengue virus.

Order No. (Anti-FSME) FormatsEI 2661-9601 G or M page 94

Antibodies against SARS CoV, TBE virus, WestNile virus.

Antibodies against Japanese encephalitis virus,Yellow fever virus, Dengue virus.

Antibodies against Sandfly fever virus, Hanta-virus, Crimean-Congo fever virus.

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FI 2821-1001-1 G FI 2822-1001-1 G

RESPIRATORY TRACT PROFILE 1 EXANTHEMA PROFILE 1IgG IgM IgG IgM

Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10

V Verification BIOCHIP*** V Verification BIOCHIP***1. RSV 1. HHV-62. Adenovirus type 3 2. Rubella virus*3. Influenza virus type A (H1N1) 3. Measles virus4. Influenza virus type A (H3N2) 4. Mumps virus

Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10

5. Influenza virus type B 5. VZV6. Parainfluenza virus type 1 6. EBV-CA**7. Parainfluenza virus type 2 7. EBV-EA8. Parainfluenza virus type 3 8. Treponema pallidum

Field C 1 : 10 1 : 10 Field C 1 : 100 1 : 10

9. Parainfluenza virus type 4 9. HSV-110. Bordetella pertussis** 10. HSV-211. Bordetella parapertussis** 11. Coxsackie virus type B112. Mycoplasma pneumoniae 12. Coxsackie virus type A9

Field D 1 : 100 1 : 10 Field D 1 : 100 1 : 1013. Coxsackie virus type B1 13. Echo virus type 714. Coxsackie virus type A7 14. Borrelia afzelii15. Echo virus type 7 15. Borrelia burgdorferi sensu stricto (CH)16. Chlamydia pneumoniae 16. Borrelia garinii

Field E 1 : 100 1 : 100 Field E 1 : 100 1 : 100

17. Haemophilus influenzae*,** 17. CMV18. Klebsiella pneumoniae* 18. Candida albicans**19. Legionella pneumophila serotype 1*,** 19. Candida krusei*,**20. Legionella pneumophila serotype 12*,** 20. Candida tropicalis*,**

FI 2823-1001-1 G FI 2824-1001-1 G

LYMPHADENITIS PROFILE 1 CENTRAL NERVOUS SYSTEM PROFILE 1IgG IgM IgG IgM

Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10

V Verification BIOCHIP*** V Verification BIOCHIP***1. HIV-1* 1. Rubella virus*2. HIV-2* 2. Measles virus3. HHV-6 3. Mumps virus4. Rubella virus* 4. VZV

Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10

5. Measles virus 5. Adenovirus type 36. Mumps virus 6. EBV-CA**7. Adenovirus type 3 7. Treponema pallidum8. Parainfluenza virus type 1 8. Toxoplasma gondii**

Field C 1 : 10 1 : 10 Field C 1 : 100 1 : 10

9. EBV-CA** 9. HSV-110. EBV-EA 10. HSV-211. Toxoplasma gondii** 11. Coxsackie virus type B112. Treponema pallidum 12. Coxsackie virus type A7

Field D 1 : 100 1 : 10 Field D 1 : 100 1 : 10

13. HSV-1 13. Echo virus type 714. HSV-2 14. Borrelia afzelii15. CMV** 15. Borrelia burgdorferi sensu stricto (CH)16. Coxsackie virus type B5 16. Borrelia garinii

Field E 1 : 100 1 : 10 Field E 1 : 100 1 : 10017. Coxsackie virus type A9 17. CMV18. Bartonella henselae** 18. Haemophilus influenzae*,**19. Chlamydia trachomatis** 19. Listeria monocytogenes 1/2a*20. Chlamydia pneumoniae 20. Listeria monocytogenes 4b*

BIOCHIP Mosaics™ for Infectious Serology(For formats see pages 149-150)

* For clinical evaluation the results must be confirmed with a CE approved test.** For practical reasons the recommended incubation differs from the standard incubation for this substrate.*** Field A contains a verification BIOCHIP. The incubation was performed correctly if the dots show a visible colour reaction.BIOCHIP Mosaics™ containing fewer substrates can be produced upon request.


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BIOCHIP Mosaics™ for Infectious Serology(For formats see pages 149-150)

FI 2825-1001-1 G FI 2826-1001-1 G

MYOCARDITIS PROFILE 1 INFECTIOUS ARTHRITIS PROFILE 1IgG IgM IgG IgM

Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10

V Verification BIOCHIP*** V Verification BIOCHIP***1. Mumps virus 1. VZV2. Adenovirus type 3 2. Influenza virus type A (H1N1)3. Influenza virus type A (H1N1) 3. Influenza virus type A (H3N2)4. Influenza virus type A (H3N2) 4. Influenza virus type B

Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10

5. Influenza virus type B 5. Yersinia enterocolitica O:3*,**6. Parainfluenza virus type 1 6. Yersinia enterocolitica O:6*,**7. Parainfluenza virus type 2 7. Yersinia enterocolitica O:9*,**8. Mycoplasma pneumoniae 8. Toxoplasma gondii**

Field C 1 : 100 1 : 10 Field C 1 : 100 1 : 109. CMV** 9. Borrelia afzelii10. Coxsackie virus type B1 10. Borrelia burgdorferi sensu stricto (CH)11. Coxsackie virus type A16 11. Borrelia garinii12. Echo virus type 7 12. Chlamydia trachomatis**

Field D 1 : 100 1 : 10

13. Borrelia afzelii14. Borrelia burgdorferi sensu stricto (CH)15. Borrelia garinii16. Chlamydia pneumoniae

FI 2827-1001-1 G FI 2828-1001-1 G

GASTROINTESTINAL TRACT PROFILE 1 ACCOMPANYING HEPATITIS PROFILE 1IgG IgM IgG IgM

Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10

V Verification BIOCHIP*** V Verification BIOCHIP***1. Adenovirus type 3 1. Adenovirus type 32. Yersinia enterocolitica O:3*,** 2. EBV-CA**3. Yersinia enterocolitica O:6*,** 3. EBV-EA4. Yersinia enterocolitica O:9*,** 4. Toxoplasma gondii**

Field B 1 : 100 1 : 10 Field B 1 : 100 1 : 10

5. Coxsackie virus type B3 5. HSV-16. Coxsackie virus type A7 6. HSV-27. Echo virus type 7 7. CMV**8. Campylobacter jejuni*,** 8. Coxsackie virus type B5

Field C 1 : 100 1 : 100 Field C 1 : 10 1 : 10

9. Campylobacter coli*,** 9. Coxsackie virus type A910. Helicobacter pylori** 10. Echo virus Typ 711. Klebsiella pneumoniae* 11. Echinococcus granulosus**12. Candida albicans**

FI 2829-1001-1 G FI 2831-1001-1 G

OPHTHALMOLOGY PROFILE 1 PREGNANCY PROFILE 1IgG IgM IgG IgM

Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10

V Verification BIOCHIP*** V Verification BIOCHIP***1. Measeles virus 1. Rubella virus*2. VZV 2. Toxoplasma gondii**3. Adenovirus type 3 3. HIV-1*4. Toxoplasma gondii** 4. HIV-2*

Field B 1 : 100 1 : 10 Field B 1 : 100 1 : 10

5. HSV-1 5. Chlamydia trachomatis**6. HSV-2 6. CMV**7. Coxsackie virus type A24 7. HSV-28. Chlamydia trachomatis** 8. VZV**

* For clinical evaluation the results must be confirmed with a CE approved test.** For practical reasons the recommended incubation differs from the standard incubation for this substrate.*** Field A contains a verification BIOCHIP. The incubation was performed correctly if the dots show a visible colour reaction.BIOCHIP Mosaics™ containing fewer substrates can be produced upon request.


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Additional Reagents for the Determination of Acute Infections

IgG Absorpion

• Before a patient’s serum is tested for specific antibodies of the IgM class, anti-bodies of class IgG must be removed by ultracentrifugation, chromatography orimmunoabsorption.

• Specifically bound IgG would displace IgM from the antigen leading to false IgMnegative test results.

• Moreover, the absorption prevents any IgM class rheumatoid factors presentfrom reacting with specifically bound IgG and thus leading to false IgM positivetest results.

• Indication: an IgG absorption of serum samples should always be performed forall IgM antibody determinations in infectious serology before incubating the sera.

EUROSORB IgG/RF Absorbent for Indirect Immunofluorescence

• Functional principle: the EUROSORB reagent contains an anti-human IgG anti-body preparation from goat. Immunoglobulin G of a serum or plasma sample isbound with high specificity by these antibodies and precipitated. If the samplealso contains rheumatoid factors, these will be absorbed by the anti-human IgG/IgG complex.

• Incubation time of the sample with the reagent is 15 minutes. A centrifugationstep for a subsequent investigation by immunofluorescence is recommended.

• All IgG subclasses are bound and precipitated by the anti-human IgG antibodies.

• Human serum IgG in concentrations of up to 15 mg/ml and rheumatoid factorsare completely removed by the absorbent (average serum IgG concentration inadults: 12 mg/ml).

• The recovery rate of the IgM fraction is almost 100%.

• One unit contains 4.5 ml absorbent, sufficient for the absorption of 100 serumsamples.

EUROSORB IgG/RF Absorbent.

rheumatoid factor

IgG

absorbent

Order No. FormatsZF 1270-0145 page 152

Order No. FormatsZF 1130 und ZF 1131 page 152

Reagents for determination of low-avidity anti-bodies in infectious serology.

Urea Solutions and Avidity Buffers for the Determination of Low-Avidity Antibodies in Infectious Serology

• To identify low-avidity antibodies in a patient’s serum, two immunofluorescencetests are performed in parallel: one test is carried out in the conventional way,the other one includes urea treatment between incubations with patient’s serumand peroxidase-labelled anti-human IgG, resulting in the detachment of low-avidity antibodies from the antigens.

• Low-avidity antibodies are present if the fluorescence intensity is significantlyreduced (two intensity levels ore more) by urea treatment.

• The following reagents for avidity determination are available:

IFT, Ab against Order No. Avidity Solution Incubation Time

Rubella ZF 1130-0501 urea solution, 5 M 10 min

WNV ZF 1130-0601 urea solution, 6 M 10 min

Toxoplasma gondii ZF 1130-0801 urea solution, 8 M 10 min

EBV-EA, EBV-CA ZF 1130-0801 urea solution, 8 M 30 min

CMV ZF 1131-0101-1 avidity buffer 1 10 min

VZV ZF 1131-0101-2 avidity buffer 2 30 min


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EUROIMMUN PRODUCTS FOR ALLERGOLOGY


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AllercoatTM 6 ELISA.AllercoatTM 6 ELISA.

EUROLINE: Specific IgE

• Determination of specific IgE in serum.

• Indication: Clarification of allergic reactions to inhalation allergens, foodallergens and cross-reactive allergens (pollen-associated food allergies).

• Serum dilution: undiluted (or 1 : 10); conjugate class anti-IgE (monoclonal), AP-labelled.

• Calibration: 3 indicator bands on each strip for semiquantitative evaluation.

• Antibodies against up to 20 allergens per strip can be simultaneously mono-specifically detected.

• EUROLINE profiles with different allergen compositions are available for varioustest requirements: atopy, inhalation, food and cross reactions.

• The program EUROLineScan from EUROIMMUN has been developed to enablequantitative evaluation of EUROLINE analyses, facilitate management of data,and provide detailed documentation of results.

• The incubated EUROLINE test strips are scanned using a flatbed scanner.EUROLineScan recognizes the position of the strips, even if they have beenplaced inexactly, identifies the bands, and measures their intensity.

Incubated EUROLINE Allergy Profile Inhalation.

EUROIMMUN Microplate ELISA: Total IgE

• Determination of the total IgE concentration in serum.

• Indications: Differentiation between allergic and intrinsic asthma, betweenallergic and vasomotor rhinitis, and between atopic and seborrhoic dermatitis.

• Serum dilution 1 : 10; conjugate class anti-IgE (monoclonal), POD-labelled.

• One microplate well incubated per patient.


• Coating: anti-human IgE, polyclonal.

• The Total IgE ELISA serves as a screening test for allergy diagnostics andprovides an indication for the presence of an allergic reaction.

Incubated ELISA Total IgE.

grasses

animal hair

trees

mould spores

weeds

indicators

mites

Antibodies of Class IgE against Allergens

Order No. (Inhalation) FormatsDP 3110-1601 E Page 82

Order No. FormatsEV 3840-9601 E Page 95

Order No. FormatsEP ####-0110 E Page 96-115

Allercoat™ 6 Microplate ELISA: Specific IgE

• Determination of allergen-specific IgE concentrations in serum.

• Indication: identification of allergic reactions to more than 600 different allergensand allergen mixtures.

• Serum dilution: undiluted, conjugate class anti-human IgE, AP-labelled.

• One microplate well per allergen/allergen mixture is incubated for each patient.

• Calibration: 6-point calibration, quantitative; using reference preparation 2 IRP75/502 from the WHO.

• The allergens are coupled to paper rings and can be flexibly configured for eachsample according to the analysis.

• Customized pre-assembled microplates with individual allergy parameters areavailable on request (Order no.: EP 9901-0101). Orders can be made online withthe provided software. Please contact us!

• A light table and special evaluation software are available to supplement thesimple manual Allercoat™ 6 ELISA procedure.

• Allercoat™ 6 ELISA are automatable using the EUROIMMUN Analyzer I and theEUROIMMUN Allercoat software.


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AllercoatTM Software.

Antibodies of Class IgE against Allergens

Customized Laboratory Software for Flexible Automation ofAllercoat™ System

• Convenient online ordering of individual pre-prepared Allercoat™ microtiterplates.

• Integrated light table for manual preparation of ELISA plates and sampledistribution.

• Direct control of photometer, automated evaluation via calibration curve andcompilation of results.

• Fully automated incubation of samples and evaluation of results via connectionto the EUROIMMUN Analyzer I.

• Fully automated administration, documentation and archiving of all data.

• Simple operation using graphic user commands and clear presentation of themost important information at a glance.

• Connection to commonly used laboratory systems for convenient transfer ofrequests and results.

• Additional security through user administration with individual access rightsand confirmation step before results editing.

Fitting of allergen rings intomicroplate wells

Incubate: 60 min, 37 °C


allergen rings

undilutedsamples

enzymeconjugate

chromogen-/substrate sol.




Evaluate: photometric measurementat a wavelength of 405 nm





stopsolution

Individual equipmentwith allergen rings


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Products from EUROIMMUN AG will be delivered according to the following conditions, as long as no other conditions have been agreed inwriting. On issuing an order, the buyer acknowledges the delivery conditions. EUROIMMUN does not accept the sales conditions of thebuyer, even when EUROIMMUN has not expressly contradicted them. Contract terms are valid for all future business connection even if theyhave not been expressly agreed upon again.

Orders: Orders to EUROIMMUN can be made in writing (including electronic communication) or verbally. Verbally issued orders firstbecome legally binding for EUROIMMUN with a written confirmation from the orderer or with the delivery of goods.

Delivery: EUROIMMUN generally delivers to end users within 7 days of order receipt and to distributors within 14 days, but is not tied toany definite delivery period. If a delivery is not possible through unforseeable circumstances (e.g., factory disruptions, raw material deliverydelays, transport difficulties, strikes), the delivery obligation does not apply. EUROIMMUN reserves the right to deliver in part. The deliveryobligation of EUROIMMUN AG ceases as long as the customer is in arrears. EUROIMMUN chooses the packing and dispatching method atits own discretion, according to the respective requirements.

Product characteristics: The delivered products comply with specifications given in the product catalogue, on the product itself, or in thesupplied information sheets. If specifications are inconsistent, the labels on the product itself and the details in the information sheetprovided with the product apply. After the given expiration date has passed, the test reagents must not be used.

EUROIMMUN products must only be used for the intended purpose. It is the buyer’s responsibility to check the functional capabilityimmediately on receipt of the product as well as on every day of usage. In particular, the functioning of test reagents can be perturbedthrough causes outside the direct influence of the maunfacturer, for example, through suboptimal transportation, incorrect storage, orincorrect usage. When test reagents delivered from EUROIMMUN are used, the user must supervise the analysis with appropriateproficiency.

Warranty and liability: If nothing else has been agreed upon in writing, all risks pass to the buyer as soon as the goods have beendelivered to the carrier or has left EUROIMMUN AG premises for dispatch. With notification of dispatch by EUROIMMUN the risk passes tothe buyer if the delivery is postponed or delayed by request of the buyer. On receipt of the goods, the buyer has one working day to checkif they are in accordance with the nature and quantity of the agreement and if the goods are free from visible defects. If any complaints arisefrom this inspection, they should be communicated to EUROIMMUN AG in writing within 2 working days. Hidden defects or functionalfaults that were not identifiable with the initial inspection and are later discovered should be communicated to EUROIMMUN AG in writingwithin 14 days of receipt of the goods. If no complaints are received within the stipulated period, it is assumed that the goods are ofappropriate quality and quantity for the customer. Complaints do not release the buyer from payment obligation.

With prompt and reasonable complaints on the grounds of product defects or the delivery of something other than the ordered goods,EUROIMMUN is obliged to exchange or amend the goods within 14 days or to withdraw or reimbourse the payment, as it chooses. If thedefect is not corrected in spite of delivery of a replacement or an amended product, the buyer can demand that the sale is cancelled.

If defects are promptly reclaimed, EUROIMMUN has the choice between a further delivery or an appropriate credit note. Furthercompensatory claims from the buyer are excluded, as long as EUROIMMUN has not violated its contractual or legal obligations throughoutright negligence or by intention. In such cases EUROIMMUN provides compensation of up to a maximum of 20 times the price of onepacket (test kit) of the defective product. EUROIMMUN takes no responsibility for any damage resulting from faulty goods.

Prices: Prices from the official EUROIMMUN pricelist in the country of the buyer are applicable. Invoices are provided in the agreedcurrency. Prices are “ex works”. Expenses for packing and freight as well as for cooling during transport are added on, including costs forthe disposal of packaging material by the customer. Statutory value added tax is not included in the list prices.

Payment terms: Payment obligations in countries of export must be settled within 30 days after recieving the goods. No cash discountswill be given unless agreed in writing. Payments by cash transfer or check are valid from the timepoint that the invoice amount is credited toa EUROIMMUN AG bank account. In cases of payment arrears, EUROIMMUN reserves the right to charge compensatory interest of 10% p.a.,applicable from the settlement date, without any further notice. In special cases EUROIMMUN can arrange alternative payment periods ordemand advance payments. EUROIMMUN’s demands resulting from an order cannot be offset by the customer through counter demands.

Ownership rights: The delivered goods remain the property of EUROIMMUN AG until full payment. Selling on of EUROIMMUN productsis only permitted for companys who are authorized in writing from EUROIMMUN to do so. Software received from EUROIMMUN should notbe passed on to third parties without written permission from EUROIMMUN AG.

Consultation: Advice from EUROIMMUN AG, although provided to the best knowledge, is nevertheless not binding. No liability claims canensue from erroneous advice.

Applicable law, place of jurisdiction, ineffective regulations: The contract conditions are subject to the laws of the Federal Republicof Germany. The United Nations Conventions on Contracts for the International Sale of Goods does not apply. The place of jurisdiction andfulfilment is Luebeck. If any provision of these general delivery conditions will be held invalid or unenforcable, this general deliverycondition will not be rendered invalid as a whole, and the provisions will be changed and interpreted so as best to accomplish the objectiveof the unenforcable or invalid provision.

General Delivery Conditions


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IndexAutoantibody Diagnosticsacetylcholine receptor (ACHR) .............................................................................................. 12, 17, 89actin ...................................................................................................... 16, 17, 32, 38, 47, 68, 122, 129adrenal cortex ........................................................................................................... 13, 17, 45, 66, 116agglutination test ................................................................................................................................ 89AMA ..................................................... 6, 13, 16-17, 26, 33, 37-40, 45, 47, 68, 79, 116, 122, 126-131amphiphysin ............................................................................................................ 17, 42, 80, 117-118ANA ......................................... 14, 16-17, 26, 32-34, 37-38, 42, 46-47, 68, 80, 87, 118-124, 126-131ANCA ................................................................ 12-14, 16-17, 32, 46-47, 66-67, 86, 119-121, 123-124aquaporin .................................................................................................................. 12, 17, 42, 66, 118ASCA ......................................................................................................... 15, 17, 76, 95, 101, 123-124ASMA ........................................................................ 12, 16-17, 37-38, 68, 117-118, 123-126, 128-131Autoantibody Profile 2 ...................................................................................................................... 128basement membrane ...................................................................... 12, 16-17, 46, 67, 80, 86, 120-121ß2-glycoprotein ................................................................................................................................... 88bile ducts ........................................................................................................................................ 17, 32BP180 ......................................................................................................................... 12, 17, 41, 87, 125BP230 ......................................................................................................................... 12, 17, 41, 87, 125BPI ....................................................................................................................................... 17, 46-47, 86brain ................................................................................................................................ 12, 66, 116-117C1q ........................................................................................................................................... 16, 87, 88cANCA ............................................................................... 12, 16-17, 32, 46-47, 66, 86, 119-121, 123cardiolipin (AMA M1) ....................................................................................................... 16-17, 84, 88cartilage ........................................................................................................................................ 16, 124cathepsin G ........................................................................................................................ 17, 46-47, 86cell nuclei (ANA global test) .... 14, 16-17,26, 32-34, 37-38, 42, 46-47, 68, 80, 87,118-124, 126-131centromere ................................................................................................ 14, 16, 32, 34, 47, 68, 87-88cerebellum .................................................................................................... 12-14, 42-44, 83, 116-118circulating immune complexes (CIC) ................................................................................... 16, 35, 88cyclic citrullinated peptide (CCP) ........................................................................................ 16, 36, 87cyclin I (PCNA) ......................................................................................... 12, 16, 26, 32, 47, 68, 80, 87cyclin II (mitosin) .................................................................................................................... 12, 47, 68cytoplasm of granulocytes ........................... 12-14, 16-17, 32, 46-47, 66-67, 86, 119-121, 123-124desmoglein ....................................................................................................... 12, 17, 41, 87, 124, 125desmosomes ............................................................................................................. 12, 17, 41, 67, 125dsDNA ...................................... 6, 12, 16-17, 26, 32-35, 38, 42, 47, 68, 79-80, 87, 89, 128, 130, 151elastase ............................................................................................................................... 17, 46-47, 86elastin ................................................................................................................................. 12, 16-17, 69ENA .................................................................................................................. 16, 24, 32, 34, 79-80, 87endomysium ....................................................................................... 12, 17, 32, 48, 69, 88, 131-133endothelial cells .................................................................................................. 12, 16-17, 32, 69, 133epidermis .................................................................................................................. 12-13, 17, 67, 125EUROArray .......................................................................................................................................... 89EUROPLUS ............. 7, 12, 32, 37-41, 46-48, 50, 52, 116, 120-123, 126-127, 129, 131-136, 140, 148eye antigens ....................................................................................................................................... 118F-actin ...................................................................................................................... 17, 38, 68, 122, 129GAD ......................................................................................................... 12, 17, 42, 44, 66, 86, 89, 116gangliosides ................................................................................................................................... 17, 80gliadin .............................................................................. 7,12, 17, 48, 69, 76, 95, 101, 131-133, 151glomerular basement membrane (GBM) .......................................... 12, 17, 46, 67, 80, 86, 120-121glutamate receptor .................................................................................................... 12, 17, 43, 66,118glutamic acid decarboxylase ............................................................... 12, 17, 42, 44, 66, 86, 89, 116Golgi apparatus .......................................................................................................... 12, 16, 32, 47, 68goblet cells ............................................................................................................... 12, 17, 67, 123-124heart muscle ................................................................................................................ 12, 17, 124, 130HEp-2-cells ................................................... 6, 12-14, 32-33, 35, 37-38, 44-45, 81, 114-118, 121-126histones ............................................................................................ 6, 13, 16, 26, 32-34, 47, 79-80, 87Hu ...................................................................................................... 13, 17, 42-43, 66, 80, 83, 116-118HUVEC ................................................................................................................................................ 133hypothalamus antigens ............................................................................................................. 13, 117IA-2 ........................................................................................................................................... 17, 44, 89insulin ...................................................................................................................................... 17, 44, 89intestinal goblet cells .............................................................................................. 12, 17, 67, 123-124intrinsic factor ............................................................................................ 13, 17, 45, 67, 86, 122-123Jo-1 .................................................................... 13, 16, 24, 26, 32-34, 47, 68, 79-80, 87-88, 126-127keratin ............................................................................................................ 12, 13, 16-17, 36, 67, 125Ku .................................................................................................................... 13, 16, 26, 33, 47, 68, 80lactoferrin .................................................................................................... 17, 46-47, 67, 86, 121, 124latex agglutination test ........................................................................................................................ 89LC-1 ............................................................................................................. 17, 26, 32, 38-39, 79-80, 83Leydig cells .............................................................................................................. 17, 43, 64, 112-113liver-kidney microsomes (LKM) ................................................. 13, 17, 37-38, 67, 116, 122, 126-131liver-specific antigens ........................................................................................ 13, 17, 32, 38, 67, 121LKM-1 ............................................................................................................... 17, 26, 32, 39, 79-80, 86lung alveoli .................................................................................................................................. 17, 121lymphocyte antigens .......................................................................................................... 13, 17, 121M2 antigen (AMA-M2) .................................................................. 6, 17, 26, 33, 37-39, 68, 79-80, 88M4 antigen .......................................................................................................... 13, 17, 32, 37, 79, 108M9 antigen ................................................................................................... 13, 17, 32, 37, 68, 79, 108Mab .................................................................................................................................. 17, 40, 66, 116MAG ................................................................................................................................... 13, 17, 42, 66Mi-2 ........................................................................................................................ 13, 16, 26, 33, 47, 80mitochondria (AMA) ....................... 6, 13, 16-17, 26, 33, 37-40, 45, 47, 68, 79, 116, 122, 126-131mitosin (cyclin II) .................................................................................................................... 12, 47, 68myelin ........................................................................................................................... 12-13, 17, 42, 66myeloperoxidase (MPO) ........................................................................ 13, 17, 46-47, 79-80, 86, 120nDNA ....................................... 6, 12, 16-17, 26, 32-35, 38, 42, 47, 68, 79-80, 87, 89, 128, 130, 151nerves ......................................................................................................... 12-14, 17, 42, 66, 117-118neuronal autoantibodies ............................................................................................ 17, 42-43, 80, 83NMDA receptor ......................................................................................................... 12, 17, 43, 66, 118NMO ....................................................................................................................................... 17, 42, 118nRNP/Sm .............................................................................. 16, 24, 26, 32-34, 47, 79-80, 87, 126-127nuclear membrane ........................................................................................................... 17, 32, 47, 68nucleosomes .............................................................................................. 16, 32-33, 35, 47, 79-80, 87oesophagus ............................................................................................... 12-13, 41, 48, 125, 131-132ovarial antigens .............................................................................................................. 45, 86, 89, 116P/Q calcium channel (VGCC) ....................................................................................................... 17, 89pANCA ......................................................................... 13, 16-17, 32, 46-47, 67, 86, 119-121, 123-124pancreas islets ................................................................................................. 114, 44-45, 66, 116, 118parathyroid gland ................................................................................................................. 13, 17, 116parietal cells (PCA) ............................................................................. 12, 17, 45, 67, 86, 116, 122-123parotid gland excretory ducts and acini .......................................................................... 14, 17, 124PCNA (cyclin I) ......................................................................................... 12, 16, 26, 32, 47, 68, 80, 87phosphatidylserine ........................................................................................................................ 16, 88phospholipids .............................................................................................................................. 16, 108pituitary gland antigens ..................................................................................................... 13, 17, 117PL-12 ............................................................................................................................ 16, 26, 33, 47, 80PL-7 .............................................................................................................................. 16, 26, 33, 47, 80placenta ................................................................................................................................ 14, 17, 117PM-Scl ..................................................................................................... 6, 16, 26, 32-34, 47, 79-80, 87proteinase 3 (PR3) ....................................................................... 7, 14, 17, 46-47, 66, 79-80, 86, 120proteinase 3 (capture test) ........................................................................................................... 46, 86renal glomeruli (GBM) ......................................................................... 12, 17, 46, 67, 80, 86, 120-121

reticulin ........................................................................................................................... 14, 17, 131-133retina ................................................................................................................................. 13-14, 17, 118rheumatoid factors ........................................................................................................................ 36, 60Ri ............................................................................................................. 17, 42-43, 66, 80, 83, 116-118RIA ................................................................................................................... 16, 30, 35, 40, 44, 86-90ribosomal P-proteins ................................................................................................. 14, 16, 32, 68, 88RNS-Polymerase ............................................................................................................... 14, 16, 32, 47Ro-52 ......................................................................................... 16-17, 26, 32-34, 39, 47, 79-80, 83, 87Sa ............................................................................................................................................. 16, 36, 87Saccharomyces cerevisiae ..................................................................... 15, 17, 76, 95, 101, 123-124Scl-70 .................................................................. 14, 16, 24, 26, 32-34, 47, 68, 79-80, 87-88, 126-127skeletal muscle ........................................................................................ 12-14, 17, 38, 122, 124, 130SLA/LP ........................................................................................................ 17, 26, 32, 38-39, 79-80, 86Sm ........................................................................... 14, 16, 24, 26, 32-34, 47, 68, 79-80, 87, 126-127smooth muscles ........................................................................... 12, 16-17, 38, 67, 117-118, 123-126Sp100 ...................................................................................................................... 17, 26, 38-39, 68, 80spermatozoa ....................................................................................................... 14, 17, 66, 86, 89, 117spindle fibers .................................................................................................................... 16, 32, 47, 68SS-A ......................................................... 6, 14, 16-17, 24, 26, 32-34, 47, 68, 79-80, 83, 87, 126-127SS-B ........................................................... 6, 14, 16-17, 24, 26, 32-34, 47, 68, 79-80, 87-88, 126-127ssDNA ..................................................................................................................... 14, 16-17, 34, 47, 87TAb ................................................................................................................................... 17, 40, 66, 116testis ............................................................................................................. 14, 17, 40, 43, 66, 116-117thrombocyte antigens .................................................................................................... 14, 17, 67, 121thyroglobulin (TG) .................................................................... 14, 17, 40, 45, 66, 79, 86, 89, 90, 116thyroid gland ......................................................................................... 14, 17, 40, 45, 66, 86, 89, 116thyroid peroxidase (TPO) .......................................................................................... 17, 40, 79, 86, 89TRAb .................................................................................................................................. 17, 40, 86, 89transglutaminase .................................................................................................................... 17, 48, 88U1-nRNP ............................................................................................................................ 14, 16, 68, 87vascular endothelium ............................................................................................................ 16, 17, 69vimentin ............................................................................................................................ 14, 16, 47, 68Yo ...................................................................................................... 14, 17, 42-43, 66, 80, 83, 116-118zona pellucida ................................................................................................................... 17, 66, 86, 89

Infectious serologyAdenovirus ................................................................................................ 15, 18, 58-59, 74-75, 94,144Afipia felis ....................................................................................................................................... 15,18Bartonella ............................................................................................................ 15, 18, 58, 71, 72, 138Bordetella ..................................................................................................... 15, 18, 58, 70, 81, 91, 134Borrelia .................................................... 15-18, 21, 28, 50-51, 58-59, 70-71, 77, 81, 84, 91, 135-136Brucella abortus .................................................................................................................................. 92Campylobacter .................................................................................................... 15, 18, 59, 70, 91, 134Candida ....................................................................................................... 15, 18, 58-59, 76, 108, 150Chikungunya virus ......................................................................................................... 15, 57, 76, 150Chlamydia .................................................................................. 15-16, 18, 56, 58-59, 71, 92, 137-138Coxsackie virus ............................................................................................ 15, 18, 58-59, 75, 145-146Crimean Congo fever virus ................................................................................................. 57, 76, 149Cytomegalovirus (CMV) ..................................................... 7, 15, 21, 58-60, 73, 81, 85, 93, 142, 151Dengue virus ............................................................................................. 15, 57, 74, 94, 143-144, 150EBNA ......................................................................................................... 15, 18, 52-53, 76,81, 95, 148EBV-CA ........................................................................ 7, 15, 18, 21, 52-53, 58-60, 75-76, 95, 147-148EBV-EA ................................................................................................ 7, 18, 52, 58-60, 76, 95, 147-148Echinococcus granulosus ................................................................................ 15, 18, 82, 88, 106, 136Echo virus ............................................................................................................ 15, 18, 58-59, 75, 146Epstein-Barr virus capsid ag ......... 7, 15, 18, 21, 52-53, 58-60, 75-76, 78, 81, 85, 95, 147-148, 152EUROPLUS ............. 7, 12, 32, 37-41, 46-48, 50, 52, 116, 120-123, 126-127, 129, 131-136, 140, 148EUROSORB IgG/RF absorbens ........................................................................................... 60, 64, 152Haemophilus influenzae .......................................................................................... 15, 18, 58, 70, 134Hantavirus ........................................................................................................... 15, 57, 75, 81, 95, 147Helicobacter pylori .......................................................................... 15, 18, 54, 59, 70, 77, 84, 91, 134Herpes simplex (HSV) ...................................... 15, 18, 21, 55, 58-59, 73, 78, 81, 85, 92-93, 140-141HHV-6 ......................................................................................................................... 15, 18, 58, 73, 141HIV ...................................................................................................... 15, 18, 36, 58-59, 72-73, 140-141Influenza virus ........................................................................ 15, 58-59, 70, 75, 94-95, 134, 144-145Japanese encephalitis virus ......................................................................................... 57, 74, 143,150Klebsiella pneumoniae ....................................................................................... 15, 18, 58-59, 70, 134Legionella .................................................................................................... 15, 18, 58, 71, 91, 136-137Leishmania ................................................................................................................ 15, 18, 57, 72, 139Listeria ....................................................................................................................... 15, 18, 58, 71, 136Measles virus .................................................................................... 15, 18, 21, 58-59, 64, 73, 93, 142Mumps virus ....................................................................................... …15, 18, 21, 58-59, 73, 93, 142Mycoplasma .................................................................................................. 15, 18, 58-59, 72, 92, 139Parainfluenza virus .............................................................................................. 15, 58-59, 75, 95, 145Parvovirus ...................................................................................................................................... 36, 93Plasmodium ........................................................................................................ 7, 15, 18, 57, 140, 150Reiter spirochetes ............................................................................................................................... 70Respiratory syncytial virus (RSV) ..................................................................... 15, 18, 58, 74, 94, 144Rift valley fever virus ........................................................................................................... 57, 74, 149Rubella virus ..................................................................... 7, 15, 18, 21, 73, 81, 85, 93, 140, 142, 149Sandfly fever viris ............................................................................................................................... 57SARS coronavirus ....................................................................................................................... 57, 142TBE virus ......................................................................................... 15, 18, 21, 48, 55, 72, 90, 138-139Toxoplasma gondii ..................................................................... 7, 15, 18, 21, 57-60, 72, 81, 92, 140Treponema pallidum .................................................................................... 15, 18, 58, 70, 77, 84, 91Ureaplasma urealyticum ............................................................................................... 15, 18, 72, 139Varicella zoster virus (VZV) ............................................................... 15, 21, 58-60, 73-74, 93-94, 143VlsE ............................................................................................ 15, 28, 50-51, 70, 81, 84, 91, 135-136West Nile virus .............................................................................................. 7, 15, 21, 57, 74, 94, 143Yellow fever virus ........................................................................................................ 57, 74, 143 -144Yersinia enterocolitica ............................................................... 15-16, 18, 59, 71, 78, 84, 91-92, 137

Allergologyanimal allergens ...................................................................................................................... 19, 98-99environmental allergens ...................................................................................................... 19,112-113food ........................................................................................................................ 19, 62, 82-83, 100-10further allergens ................................................................................................................................ 110grasses ..................................................................................................................................... 19, 62,107herbal and flower pollen ...................................................................................... 19, 62, 102, 114-115house dust ................................................................................................................................... 19, 108insects ..................................................................................................... 19, 39, 48, 83, 86, 88, 95, 108mites ................................................................................................................................ 19, 62, 98, 108moulds .................................................................................................................................... 19,108-110parasites ................................................................................................................................... 18-19,110pharmaceutical drugs ............................................................................................................. 19, 96-97trees ...................................................................................................................................... 19, 110-111

AutomationEUROBlotMaster ...................................................................................................................... 26-27, 29EUROIMMUN Analyzer ........................................................................................................... 22, 62-63EUROLineScan ............................................................................................................... 4, 26-29, 51, 62EUROStar ............................................................................................................................................... 8instruments ............................................................................................................................... 8, 22, 27


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