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ABO Blood Group System. Importance of ABO system. ABO compatibility between donor cell and patient serum is the essential foundation of pretransfusion testing It is the only system with expected antibodies Whether they are IgG or IgM, ABO antibodies can activate complement readily - PowerPoint PPT Presentation
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ABO Blood Group SystemABO Blood Group System
Importance Importance of ABO systemof ABO system
ABO compatibility between donor cell and patient serum is the essential foundation of pretransfusion testing
It is the only system with expected antibodies Whether they are IgG or IgM, ABO antibodies
can activate complement readily– This means that incompatibilities can cause life
threatening situations (transfusion reactions)
ABO antigensABO antigens
Biochemical & Genetic Biochemical & Genetic ConsiderationsConsiderations
ABO and H Antigen GeneticsABO and H Antigen Genetics
Genes at three separate loci control the occurrence and location of ABO antigens.
The presence or absence of the A, B, and H antigens is controlled by the H and ABO genes.
The presence or absence of the ABH antigens on the red blood cell membrane is controlled by the H gene.
The presence or absence of the ABH antigens in secretions is indirectly controlled by the Se gene.
ABO Antigen GeneticsABO Antigen Genetics
H gene – H and h alleles.
Se gene – Se and se alleles.
ABO genes – A, B and O alleles.
H AntigenH Antigen
The H gene codes for an enzyme that adds the sugar fucose to the terminal sugar of a precursor substance (PS)
The precursor substance (proteins and lipids) is formed on an oligosaccharide chain (the basic structure)
Type I and Type II PrecursorsType I and Type II Precursors
There are two potential precursors substances for ABH antigens Type I and Type II
Both are comprised of identical sugars but the linkage of the terminal sugars differs in the two types
Type I precursor has a terminal galactose linked to a subterminal N-acetylgluosamine in a 1-3 linkage
These same sugars combine in a 1-4 linkage in type II precursor
ABH Ags on red cells are derived from Type II chains whereas the ABH Ags in plasma are made from both types I & II precursors
Type II HType II H
After fucose is added to Type II chains, the structure is termed Type II H
Four kinds of Type II H have been identified
H1, H2 are simple straight chain glycolipidsWhereas H3 & H4 have branched chains
RBC Precursor StructureRBC Precursor Structure
Glucose
Galactose
N acetylglucosamine
Galactose
Precursor Substance (stays the
same)
RBC
Formation of the H antigenFormation of the H antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
H antigen
RBC
Fucose
H antigenH antigen
The H antigen is the foundation upon which A and B antigens are built
A and B genes code for enzymes that add a sugar to the H antigen– Immunodominant sugars are present at the
terminal ends of the chains and confer the ABO antigen specificity
A and B AntigenA and B Antigen
The “A” gene codes for an enzyme (transferase) that adds N-acetylgalactosamine to the terminal sugar of the H antigen
– N-acetylgalactosaminyltransferase
The “B” gene codes for an enzyme that adds D-galactose to the terminal sugar of the H antigen
– D-galactosyltransferase
Formation of the A antigenFormation of the A antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
RBC
Fucose N-acetylgalactosamine
Formation of the B antigenFormation of the B antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
RBC
FucoseGalactose
GeneticsGenetics
The H antigen is found on the RBC when you have the Hh or HH genotype, but NOT from the hh genotype
The A antigen is found on the RBC when you have the Hh, HH, and A/A, A/O, or A/B genotypes
The B antigen is found on the RBC when you have the Hh, HH, and B/B, B/O, or A/B genotypes
H antigenH antigen
Certain blood types possess more H antigen than others:
O>A2>B>A2B>A1>A1B
Greatest amount of H
Least amount of H
The O alleleThe O allele
Why do Group O individuals have more H antigen than the other groups?
The O gene is a silent allele. It does not alter the structure of the H substance….that means more H antigen sites.
Group O Group A
Many H antigen sites
Most of the H antigen sites in a Group A individual have been
converted to the A antigen
Fewer H antigen
sites
A
A A
AA
Group O Group A
ABO SubgroupsABO Subgroups
ABO subgroups differ in the amount of antigen present on the red blood cell membrane– Subgroups have less antigen
Subgroups are the result of less effective enzymes. They are not as efficient in converting H antigens to
A or B antigens (fewer antigens are present on the RBC)
Subgroups of A are more common than subgroups of B
Subgroups of ASubgroups of A
The 2 principle subgroups of A are: A1 and A2
– Both react strongly with reagent anti-A
– 80% of group A or AB individuals are subgroup A1
– 20% are A2 and A2B
AA22 Phenotype Phenotype
Why is the A2 phenotype important?– A2 and A2B individuals may produce an anti-A1
– This may cause discrepancies when a crossmatch is done (incompatibility)
What’s the difference between the A1 and A2 antigen?– It’s quantitative– The A2 gene doesn’t convert the H3 & H4 to A very well
– The result is fewer A2 antigen sites compared to the many A1 antigen sites
AA11 and A and A22 Subgroups Subgroups
Anti-A antisera
Anti-A1 antisera
Anti-H lectin
ABO antibodies in
serum
#of antigen sites per
RBC
A14+4+0Anti-B900 x103
A24+03+Anti-B &
anti-A1
250 x103
Other A subgroupsOther A subgroups
There are other additional subgroups of A– Aint (intermediate), A3, Ax, Am, Aend, Ael, Abantu
A3 red cells cause mixed field agglutination when polyclonal anti-A or anti-A,B is used
Mixed field agglutination appears as small agglutinates with a background of unagglutinated RBCs
They may contain anti-A1
B SubgroupsB Subgroups
B subgroups occur less than A subgroups B subgroups are differentiated by the type of
reaction with anti-B, anti-A,B, and anti-H B3, Bx, Bm, and Bel
Other ABO conditionsOther ABO conditions
Bombay Phenotype (Oh) Inheritance of hh The h gene is an amorph and results in little or
no production of L-fucosyltransferase Originally found in Bombay (now Mumbai) Very rare
BombayBombay
The hh causes NO H antigen to be produced Results in RBCs with no H, A, or B antigen
(patient types as O) Bombay RBCs are NOT agglutinated with anti-A,
anti-B, or anti-H (no antigens present) Bombay serum has strong anti-A, anti-B and anti-
H, agglutinating ALL ABO blood groups What blood ABO blood group would you use to
transfuse this patient??
ANSWERANSWER::
Another Bombay– Group O RBCs cannot be given because they still have
the H antigen– You have to transfuse the patient with blood that
contains NO H antigen
ABO Blood GroupABO Blood Group
ABO AntibodiesABO Antibodies
ABO Blood Group SystemABO Blood Group System
The ABO Blood Group System was the first to be identified and is the most significant for transfusion practice
It is the ONLY system that the reciprocal antibodies are consistently and predictably present in the sera of people who have had no exposure to human red cells
Blood Group SystemsBlood Group Systems
Most blood group systems (ABO and others) are made up of:– An antigen on a red cell and the absence of it’s
corresponding antibody in the serum (if you’re A, you don’t have anti-A)
If you do NOT have a particular antigen on your red cells then it is possible (when exposed to foreign RBCs) to illicit an immune response that results in the production of the antibody specific for the missing antigen
ABOABO
Remember:– The ABO Blood Group System does NOT require the
presence of a foreign red blood cell for the production of ABO antibodies
– ABO antibodies are “non-red blood cell stimulated” probably from environmental exposure and are referred to as “expected antibodies”
– Titer of ABO Abs is often reduced in elderly and in patients with hypogammaglobulinemia
– Infants do not produce Abs until 3-6 months of age
ABO antibodiesABO antibodies
RBC PhenotypeFrequency(%) Serum Ab
A43Anti-B
B9Anti-A
AB4--------
O44 Anti-A,B
ABO antibodiesABO antibodies
IgM is the predominant antibody in Group A and Group B individuals– Anti-A– Anti-B
IgG (with some IgM) is the predominant antibody in Group O individuals– Anti-A,B (with some anti-A and anti-B)
ABO antibody factsABO antibody facts
Complement can be activated with ABO antibodies (mostly IgM, some IgG)
High titer: react strongly (4+)
Anti-A, Anti-B, Anti-A,B
Clinically Significant
Yes
Abs class
IgM, less IgG
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
YesYes
ABO AntibodiesABO Antibodies
Usually present within the first 3-6 months of life Stable by ages 5-6 years Decline in older age & in hypogammaglobulinemia Newborns may passively acquire maternal antibodies
(IgG crosses placenta)
Nature of antibodiesNature of antibodies
Non-red blood cell stimulated – ABO antibodies
Red blood cell stimulated– Antibodies formed as a result of transfusion, etc– Usually IgG– Active at 37°C– Can occur in group O (may occur in group A or B)– These antibodies also occur in the other Blood
Group Systems
Anti-A,BAnti-A,B
Found in the serum of group O individuals Reacts with A, B, and AB cells Predominately IgG, with small portions being
IgM Anti-A,B is one antibody, it is not a mixture of
anti-A and anti-B antibodies
Anti-AAnti-A11
Group O and B individuals contain anti-A in their serum
However, the anti-A can be separated into different components: anti-A and anti-A1
Anti-A1 only agglutinates the A1 antigen, not the A2 antigen
There is no anti-A2.
Anti-A1
Clinically Significant
Sometimes
Abs class
IgM
Thermal range
4 - 22
HDNB
No
Transfusion Reactions
ExtravascularIntravascular
NoRare
Anti-HAnti-H
Auto-Anti-H
Clinically Significant
No
Abs class
IgM
Thermal range
4 - 15
HDNB
No
Transfusion Reactions
ExtravascularIntravascular
NoNo
Allo-Anti-H
Clinically Significant
Yes
Abs class
IgM, IgG
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
YesYes
ABO Antigens in SecretionsABO Antigens in Secretions
Secretions include body fluids like plasma, saliva, synovial fluid, etc
Blood Group Substances are soluble antigens (A, B, and H) that can be found in the secretions.
This is controlled by the H and Se genes
Secretor StatusSecretor Status
The secretor gene consists of 2 alleles (Se and se) The Se gene is responsible for the expression of
the H antigen on glycoprotein structures located in body secretions
If the Se allele is inherited as SeSe or Sese, the person is called a “secretor”– 80% of the population are secretors
SecretorsSecretors
Secretors express soluble forms of the H antigen in secretions that can then be converted to A or B antigens (by the transferases)
Individuals who inherit the sese gene are called “nonsecretors”– The se allele is an amorph (nothing expressed)– sese individuals do not convert antigen precursors to H
antigen and has neither soluble H antigen nor soluble A or B antigens in body fluids
Secretor Status SummarySecretor Status Summary
The Se gene codes for the presence of the H antigen in secretions, therefore the presence of A and/or B antigens in the secretions is contingent on the inheritance of the Se gene and the H gene
Se gene (SeSe or Sese)
H antigen in secretions
A antigen
B antigen
se gene (sese)
No antigens secreted in saliva or other
body fluids
and/or
ABO GroupABH
Substances
Secretors (SeSe or Sese):ABH
A+++0+
B0++++
O00+++
AB+++++++
Non-secretors (sese):
A, B, O, and AB000
Sese + h/h (no H antigen) no antigens in secretions