Download ABO Blood Group System

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
–
This means that incompatibilities can cause life
threatening situations (transfusion reactions)
ABO antigens
Biochemical & Genetic
Considerations
ABO and H Antigen Genetics
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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 Genetics

H gene – H and h alleles.

Se gene – Se and se alleles.

ABO genes – A, B and O alleles.
H 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 Precursors

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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 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 glycolipids
 Whereas H3 & H4 have branched chains
RBC Precursor Structure
RBC
Glucose
Precursor
Substance
(stays the
same)
Galactose
N acetylglucosamine
Galactose
Formation of the H antigen
RBC
Glucose
Galactose
H antigen
N-acetylglucosamine
Galactose
Fucose
H 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 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 Dgalactose to the terminal sugar of the H antigen
–
D-galactosyltransferase
Formation of the A antigen
RBC
Glucose
Galactose
N-acetylglucosamine
Galactose
Fucose
N-acetylgalactosamine
Formation of the B antigen
RBC
Glucose
Galactose
N-acetylglucosamine
Galactose
Fucose
Galactose
Genetics

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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 antigen

Certain blood types possess more H antigen than
others:
Greatest
amount of H
O>A2>B>A2B>A1>A1B
Least amount
of H
The 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.
A
A
Group O
Group A
A
Group O
Many H
antigen sites
A
Group A
Fewer
H antigen
sites
A
Most of the H antigen sites in a
Group A individual have been
converted to the A antigen
ABO Subgroups
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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 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
A2 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
A1 and A2 Subgroups
Anti-A
antisera
Anti-A1
antisera
Anti-H
ABO
# of antigen
lectin antibodies in
sites per
serum
RBC
A1
4+
4+
0
Anti-B
900 x103
A2
4+
0
3+
Anti-B &
anti-A1
250 x103
Other A subgroups

There are other additional subgroups of A
–
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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 Subgroups
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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 conditions
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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
Bombay
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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 antiH, agglutinating ALL ABO blood groups
What blood ABO blood group would you use to
transfuse this patient??
ANSWER:

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 Group
ABO Antibodies
ABO 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 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
ABO

Remember:
–
–
–
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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 antibodies
RBC Phenotype Frequency (%)
Serum Ab
A
43
Anti-B
B
9
Anti-A
AB
4
--------
O
44
Anti-A,B
ABO antibodies

IgM is the predominant antibody in Group A and
Group B individuals
–
–
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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 facts
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
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
Extravascular
Intravascular
Yes
Yes
ABO Antibodies
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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 antibodies
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
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,B
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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-A1

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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
Extravascular
Intravascular
No
Rare
Anti-H
Auto-Anti-H
Allo-Anti-H
Clinically
Significant
No
Abs class
IgM
Clinically
Significant
Yes
Abs class
IgM, IgG
Thermal range
4 - 15
HDNB
No
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
Transfusion Reactions
Extravascular
Intravascular
Extravascular
Intravascular
No
No
Yes
Yes
ABO Antigens in Secretions
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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 Status
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
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
Secretors


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 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
A antigen
Se gene
(SeSe or Sese)
se gene
(sese)
H antigen in
secretions
and/or
B antigen
No antigens secreted
in saliva or other
body fluids
ABH
Substances
ABO Group
Secretors (SeSe or Sese):
A
B
H
A
+++
0
+
B
0
+++
+
O
0
0
+++
AB
+++
+++
+
0
0
0
Non-secretors (sese):
A, B, O, and AB
Sese + h/h (no H antigen)  no antigens in secretions