Institute of Clinical Biochemistry and Laboratory ...ukb.lf1.cuni.cz/ppt/sml04.pdf · TEST INTERPRETATION PROFESIONAL EDUCATION 4. CS markers NEG Enterobiopsy CS markers POZ AGA,

SEROLOGY MARKERS IN THE SCREENING AND DIAGNOSTICS

OF COELIAC DISEASE

SEROLOGY MARKERS IN THE SEROLOGY MARKERS IN THE SCREENING AND DIAGNOSTICS SCREENING AND DIAGNOSTICS

OF COELIAC DISEASEOF COELIAC DISEASE

Petr Kocna M.D., Ph.D.http://www.lf1.cuni.cz/~kocna/pkweb1.htm

Petr Kocna Petr Kocna M.D., Ph.D.M.D., Ph.D.http://www.lf1.cuni.cz/~kocna/pkweb1.htmhttp://www.lf1.cuni.cz/~kocna/pkweb1.htm

Swiss MedLab - Lucerne, October 9, 2004Swiss MedLabSwiss MedLab -- LucerneLucerne, , October 9,October 9, 20042004

Institute of Clinical Biochemistry and Laboratory Diagnostics1st Faculty of Medicine, Charles University

General Faculty Hospital, PragueCzech Republic

Institute of Clinical Biochemistry and Laboratory DiagnosticsInstitute of Clinical Biochemistry and Laboratory Diagnostics11st Faculty of Medicine, Charles Universityst Faculty of Medicine, Charles University

General Faculty Hospital, PragueGeneral Faculty Hospital, PragueCzech RepublicCzech Republic

LIFELONG DISEASE, PERMANENT INTESTINALINTOLERANCE OF GLUTEN, PROLAMIN PROTEINS

GENETIC FACTORS - HLA-B8, HLA-DR3, HLADQ2

INITIALISING FACTORS - GLIADIN OR SIMILAR PEPTIDES

IMMUNOLOGY RESPONSE, AUTOIMMUNE TYPE OFDISEASE

DAMAGE OF SMALL INTESTINAL MUCOSA

MALABSORPTION SYNDROME

RESPONSE TO GLUTEN-FREE DIET

LIFELONG DISEASE, PERMANENT INTESTINALINTOLERANCE OF GLUTEN, PROLAMIN PROTEINS

GENETIC FACTORS - HLA-B8, HLA-DR3, HLADQ2

INITIALISING FACTORS - GLIADIN OR SIMILAR PEPTIDES

IMMUNOLOGY RESPONSE, AUTOIMMUNE TYPE OFDISEASE

DAMAGE OF SMALL INTESTINAL MUCOSA

MALABSORPTION SYNDROME

RESPONSE TO GLUTEN-FREE DIET

WHAT IS COELIAC DISEASEWHAT IS COELIAC DISEASEWHAT IS COELIAC DISEASE

SEROLOGY MARKERS OF COELIAC DISEASE Kocna P.SEROLOGY MARKERS OF COELIAC DISEASE SEROLOGY MARKERS OF COELIAC DISEASE Kocna P.Kocna P.

22

HIGH RISK OF COELIAC DISEASEHIGH HIGH RIRISSKK OFOF CCOELIAC DISEASEOELIAC DISEASE

33

05

101520253035404550

NON GE F2 F105

101520253035404550

NON GE F2 F1Thorpe, Arch.Intern.Med. Febr. 2003, 163: 286Thorpe, Arch.Intern.Med. Febr. 2003, 163: 286

1 : 22 RELATIVES 1. DEGREE1 : 39 RELATIVES 2. DEGREE1 : 56 GE SYMPTOMATOLOGY PATIENTS1 : 133 GENERAL POPULATION

1 : 22 RELATIVES 1. DEGREE1 : 39 RELATIVES 2. DEGREE1 : 56 GE SYMPTOMATOLOGY PATIENTS1 : 133 GENERAL POPULATION



CONSULTATIVE ROLE OF LABORATORYCONSULTATIVE ROLE OF LABORATORYCONSULTATIVE ROLE OF LABORATORY

SCREENINGSCREENINGSELECTIONSELECTION

TESTTESTINTERPRETATIONINTERPRETATION

PROFESIONALPROFESIONALEDUCATIONEDUCATION

44

CS markers NEG

Enterobiopsy

CS markers POZ

AGA, AGG, EmA, atTGserological markers

Low riskscreening

asymptomatic population

CS excluded

EmA / atTG NEGHistology NEG

Other dg.confirmed

Other dg.excluded

Mucosal atrophyother causes

EmA / atTG NEGHistology POZ

CS confirmed

EmA / atTG POZHistology POZ

Histology POZ

Re - Biopsy

EmA / atTG POZHistology NEG

Serology &enterobiopsy

High risksusp. CS, CS in family

malabsorption syndrome

55 Farrell - Am.J.Gastroent. Dec. 2001Farrell - Am.J.Gastroent. Dec. 2001


DIAGNOSTIC ALGORITHM FOR COELIAC DISEASEDIAGNOSTIC ALGORITHM FOR COELIAC DISEASE

1616

HLA-DQ - HLA-DQ +

HLA - DQ

HLA-DQ - HLA-DQ +

HLA - DQ

Markers - AGA IgA+ only AGA,atTG,EmA IgG+AGA,atTG,EmA IgA -

AGA,atTG,EmA IgA+

Serology screeningAGA-A, AGA-GatTG-A, atTG-GEmA-A, EmA-G

Markers - AGA IgA+ only AGA,atTG,EmA IgG+AGA,atTG,EmA IgA -

AGA,atTG,EmA IgA+

Serology screeningAGA-A, AGA-GatTG-A, atTG-GEmA-A, EmA-G

HLA-DQ - HLA-DQ +

HLA - DQ

HLA-DQ - HLA-DQ +

HLA - DQ

HLA-DQ - HLA-DQ +

Normalmucosa

Flat, atrophicmucosa

Enterobiopsy

HLA-DQ - HLA-DQ +

Normalmucosa

Flat, atrophicmucosa

Enterobiopsy

CS excludedCS excludedCS excluded

CS confirmedCS confirmedCS confirmedNormal foodRe - testing

Normal foodNormal foodRe Re -- testingtesting Latent CSLatent CSLatent CS

IgA lowIgA defficiency

IgA normal

Serum IgA

IgA lowIgA defficiency

IgA normal

Serum IgA



0.9160.9160.9400.9400.8880.8880.9040.9040.9300.930hr-atTGhr-atTG

0.7690.7690.8800.8800.6820.6820.6870.6870.8770.877gp-atTGgp-atTG

0.8910.8910.8710.8710.9250.9250.9500.9500.8130.813EmAEmA

0.6950.6950.9490.9490.6040.6040.4620.4620.9700.970AGA-A/AGA-GAGA-A/AGA-G

ACCACCNPVNPVPPVPPVSPSPSNSN

sensitivity (SN), specificity (SP)pos.predictive value (PPV), neg.predictive value (NPV)

accuracy (ACC)

sensitivity (SN), specificity (SP)pos.predictive value (PPV), neg.predictive value (NPV)

accuracy (ACC)

LABORATORY ACCURACY OF CS MARKERSLABORATORY ACCURACY OF CS MARKERSLABORATORY ACCURACY OF CS MARKERS

Kocna - Clin. Chem. Lab. Med., May 2002, 40: 485 - 492Kocna - Clin. Chem. Lab. Med., May 2002, 40: 485 - 49277




RISK PATIENTSRISK PATIENTSTEST PROCEDURETEST PROCEDURE



88






99

COELIAC SCREENING STUDY DESIGN COELIAC COELIAC SCREENINSCREENING STUDY DESIGN G STUDY DESIGN


10 YEAR STUDY WITH SEROLOGICAL MARKERS OF CS

6023 SAMPLES ANALYSED BY ELISA AND IF

483 PATIENTS ANALYSED BY BIOPSY AND HISTOLOGY

208 PATIENTS WITH CS CONFIRMED BY HISTOLOGY

EmA NEGATIVITY - 25.7% (SENSITIVITY 74.3% ONLY), 1:20

anti-tTG NEGATIVITY - 16.6% (SENSITIVITY IS 83.4%)

AGA-A or AGA-G POSITIVITY - 92.3%, WITH a-GLIADIN

10 YEAR STUDY WITH 10 YEAR STUDY WITH SEROLOGICSEROLOGICALAL MARKERMARKERS OFS OF CSCS

60236023 SAMPLESSAMPLES ANALYSED BY ELISA AND IFANALYSED BY ELISA AND IF

483483 PAPATTIENTIENTSS ANALYSED BYANALYSED BY BIOPSY AND BIOPSY AND HISTOLOGYHISTOLOGY

208208 PAPATTIENTIENTSS WITHWITH CS CONFIRMED BY CS CONFIRMED BY HISTOLOGYHISTOLOGY

EmAEmA NEGATIVNEGATIVITYITY -- 2255..77% (SEN% (SENSSITIVITITIVITYY 7744..33%% ONLYONLY)), 1:20, 1:20

antianti--tTGtTG NEGATIVNEGATIVITYITY -- 1166..66% (SEN% (SENSSITIVITITIVITYY IS IS 8833..44%)%)

AGAAGA--A oA orr AGAAGA--GG POPOSSITIVITIVITYITY -- 9922..33%%, WITH a, WITH a--GLIADINGLIADIN

1010

260 EmA + 219 EmA -

479 atTG +

20 EmA + 1392 EmA -

1412 atTG -

1891 AGA/AGG +

11 EmA + 103 EmA -

114 atTG +

5 EmA + 2385 EmA -

2490 atTG -

2604 AGA/AGG -

4495 samples

260 EmA + 219 EmA -

479 atTG +

20 EmA + 1392 EmA -

1412 atTG -

1891 AGA/AGG +

11 EmA + 103 EmA -

114 atTG +

5 EmA + 2385 EmA -

2490 atTG -

2604 AGA/AGG -

4495 samples

SCREENING STRATEGY WITH atTGSCREENINSCREENING STRATEGY WITH atTGG STRATEGY WITH atTGAGA IgAAGA IgGatTG IgAEmA IgA

AGA IgAAGA IgAAGA IgGAGA IgGatTG IgAatTG IgAEmA IgAEmA IgA


BiopsyBiopsyBiopsy

666

222

111

111

45/12745/12745/127

27/5327/5327/53

666

555555

15/12715/12715/127

555

333

13/12513/12513/125

6/1276/1276/127

2/532/532/53

4/194/194/19

97/12597/12597/125

NNNHLHLHL

CSRCSRCSRCSFCSFCSF

54/12754/12754/127

191919

6/196/196/19

222

1111

LONG-TIME PATIENT'S FOLLOW-UPLONG-TIME PATIENT'S FOLLOW-UPSEROLOGY MARKERS OF COELIAC DISEASE Kocna P.SEROLOGY MARKERS OF COELIAC DISEASE SEROLOGY MARKERS OF COELIAC DISEASE Kocna P.Kocna P.

Case: J.H. *1947, long life GFD, CS refractery, not-responding typeCaseCase: : J.H. *1947, J.H. *1947, long life GFDlong life GFD, CS refra, CS refracctertery, noty, not--responding typeresponding type

Biopsies: 1989 CS-active, florid, 1990 collagen sprue, 1991 CS-RBBiopsieiopsiess: 1989 CS: 1989 CS--active, active, florid, 1990 florid, 1990 ccoolllagen sprue, 1991 CSlagen sprue, 1991 CS--RR1212

0

50

100

150

200

250

300

350

400

1996 1997 1998 1999 2000 2001 2002 20030

50

100

150

200

250

300

350

400

1996 1997 1998 1999 2000 2001 2002 2003

cut-off levelcutcut--off leveloff level

EB: CS-REB: CSEB: CS--RR

EmA +atTG +EmA +EmA +atTG +atTG +

EB: CS-FlEB: CSEB: CS--FlFl

EmA +atTG -EmA +EmA +atTG atTG --


EmA -atTG -EmA EmA --atTG atTG --

EmA +atTG +EmA +EmA +atTG +atTG +


AGA IgAAGA IgGatTG IgA

AGA IgAAGA IgAAGA IgGAGA IgGatTG IgAatTG IgA


LONG-TIME PATIENT'S FOLLOW-UPLONG-TIME PATIENT'S FOLLOW-UPCase: M.R. *1974, CS in remision, Duhring dermatitis 9 years, non-dietCaseCase: : M.R. *1974, CS M.R. *1974, CS inin remisiremisionon, Duhring dermatitis, Duhring dermatitis 9 years, non9 years, non--dietdiet

1313

0

20

40

60

80

100

120

1996 1997 1998 1999 2000 2001 2002 20030

20

40

60

80

100

120

1996 1997 1998 1999 2000 2001 2002 2003


EB: CS-RHLA, DHEB: CSEB: CS--RRHLA, DHHLA, DH









LONG-TIME PATIENT'S FOLLOW-UPLONG-TIME PATIENT'S FOLLOW-UPCase: J.V. *1946, active sprue confirmed in every biopsy, on GFD CaseCase: : J.V. *1946, J.V. *1946, activeactive sprue sprue confirmed inconfirmed in everyevery biopsbiopsyy, on GFD , on GFD

0

50

100

150

200

250

1996 1997 1998 1999 2000 2001 2002 20030

50

100

150

200

250

1996 1997 1998 1999 2000 2001 2002 2003




EmA +atTG +EmA +EmA +atTG atTG ++

EmA -atTG +EmA EmA --atTG atTG ++

EmA +atTG +EmA +EmA +atTG atTG ++





1414








LABORATORYLABORATORYDATA ANALYSISDATA ANALYSIS


1515






1616


Medline on-lineLast referencesMedline onMedline on--linelineLast referencesLast references

Labor.methodnational registryLabor.methodLabor.method

national registrynational registry

WWW link - http://gelab.zde.czWWW link WWW link -- http://http://gelab.zde.czgelab.zde.cz1177

WWW INTERNET - GE ENCYCLOPEDYWWW INTERNET - GE ENCYCLOPEDY

http://www.azi.cz/

http://www.azi.cz/

http://www.azi.cz/


1818

EDUCATIONAL CD-ROMSEDUCATIONAL CD-ROMS

5 YEARS WE AREPRODUCING EDUCATIONAL

CD-ROM DOCUMENTS

5 YEARS WE ARE5 YEARS WE AREPRODUCING EDUCATIONALPRODUCING EDUCATIONAL

CDCD--ROM DOCUMENTSROM DOCUMENTS

EDUCATIONAL AND TEACHING ACTIVITIES IN 2004 WERE AWARDED BY

CZECH SOCIETY OF CLINICAL BIOCHEMISTRY

EDUCATIONAL AND TEACHING ACTIVITIES EDUCATIONAL AND TEACHING ACTIVITIES IN 2004 WERE AWARDED BYIN 2004 WERE AWARDED BY

CZECH SOCIETY OF CLINICAL BIOCHEMISTRYCZECH SOCIETY OF CLINICAL BIOCHEMISTRY


EXPERT GROUP FOR COELIAC DISEASEEXPERT GROUP FOR COELIAC DISEASE

MINISTRY OF HEALTH OF THE CZECH REPUBLICASSIGNATED IN MAY 2004

EXPERT GROUP FOR COELIAC DISEASE

CO-OPERATING PROFESSIONALS:

CZECH SOCIETY OF GASTROENTEROLOGYCZECH PEDIATRIC SOCIETY

CZECH SOCIETY OF CLINICAL BIOCHEMISTRYCZECH SOCIETY OF ALERGOLOGY AND IMMUNOLOGY

CZECH COELIAC PATIENTS GROUP

MINISTRY OF HEALTH OF THE CZECH REPUBLICMINISTRY OF HEALTH OF THE CZECH REPUBLICASSIGNATED IN MAY 2004ASSIGNATED IN MAY 2004

EXPERT GROUP FOR COELIAC DISEASEEXPERT GROUP FOR COELIAC DISEASE

COCO--OPERATING PROFESSIONALS:OPERATING PROFESSIONALS:

CZECH SOCIETY OF CZECH SOCIETY OF GASTROENTEROLOGYGASTROENTEROLOGYCZECH CZECH PEDIATRICPEDIATRIC SOCIETYSOCIETY

CZECH SOCIETY OF CZECH SOCIETY OF CLINICAL BIOCHEMISTRYCLINICAL BIOCHEMISTRYCZECH SOCIETY OF CZECH SOCIETY OF ALERGOLOGY AND IMMUNOLOGYALERGOLOGY AND IMMUNOLOGY

CZECH CZECH COELIAC PATIENTSCOELIAC PATIENTS GROUPGROUP

1919






LABORATORYLABORATORYDATA ANALYSISDATA ANALYSIS


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2020


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Institute of Clinical Biochemistry and Laboratory ...ukb.lf1.cuni.cz/ppt/sml04.pdf · TEST INTERPRETATION PROFESIONAL EDUCATION 4. CS markers NEG Enterobiopsy CS markers POZ AGA,