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ABO Blood Group
System
History: Karl Landsteiner


Discovered the ABO Blood Group
System in 1901
He and his five co-workers began
mixing each others red cells and serum
together and inadvertently performed
the first forward and reverse ABO
groupings
Why is it important?



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

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 (h is an amorph)

Se gene – Se and se alleles (se is an
amorph)

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)
RBC Precursor Structure
RBC
Glucose
Precursor
Substance
(stays the
same)
Galactose
N-acetylglucosamine
Galactose
Formation of the H antigen
RBC
Glucose
H antigen
Galactose
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
D-galactose 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



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
A
A
Group O
Many H
antigen sites
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 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 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
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
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

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Both react strongly with reagent anti-A
To distinguish A1 from A2 red cells, the lectin
Dolichos biflorus is used (anti-A1)
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?
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
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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 Anti-A1 Anti-H
antisera antisera lectin
ABO
antibodies
in serum
# of
antigen
sites per
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 Lfucosyltransferase
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
anti-H, 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
Landsteiner’s Rule:

Normal, Healthy
individuals possess
ABO antibodies to
the ABO antigen
absent from their
RBCs
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:

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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
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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
A
Frequency
(%)
43
Serum Ab
B
9
Anti-A
AB
4
--------
O
44
Anti-A,B
Anti-B
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-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
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-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