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

Galactose
Precursor
Substance
(stays the N-acetylglucosamine
same)
Galactose
Formation of the H antigen

RBC

Glucose

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

N-acetylgalactosamine
Fucose
Formation of the B antigen

RBC

Glucose

Galactose

N-acetylglucosamine

Galactose

Galactose
Fucose
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 Group A

Many H Fewer A
antigen sites H antigen
sites

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
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 H antigen in and/or
(SeSe or Sese) secretions B antigen

se gene No antigens secreted

(sese) in saliva or other
body fluids
 ABH
ABO Group
Substances
Secretors (SeSe or Sese): A B H

A +++ 0 +

B 0 +++ +

O 0 0 +++

AB +++ +++ +
Non-secretors (sese):
A, B, O, and AB 0 0 0

Sese + h/h (no H antigen) no antigens in secretions

Type 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 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
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
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)
Whats the difference between the A1 and A2
antigen?
Its quantitative
The A2 gene doesnt 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 ABO # of

antisera antisera lectin antibodies antigen
in serum sites per
RBC
A1 4+ 4+ 0 Anti-B 900 x103

A2 4+ 0 3+ Anti-B & 250 x103

anti-A1
 Other 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 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 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
Bombay
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
Landsteiners 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:
An antigen on a red cell and the absence of its
corresponding antibody in the serum (if youre A,
you dont 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:
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 Frequency Serum Ab

Phenotype (%)
A 43 Anti-B

B 9 Anti-A

AB 4 --------

O 44 Anti-A,B
Anti-A1
Group O and B individuals
Anti-A1
contain anti-A in their serum Clinically Abs class
However, the anti-A can be Significant IgM
separated into different Sometimes
components: anti-A and
Thermal HDNB
anti-A1
range No
Anti-A1 only agglutinates the
4 - 22
A1 antigen, not the A2
antigen Transfusion Reactions
There is no anti-A2. Extravascular Intravascular

No Rare
Anti-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
ABO 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 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 Abs class
Yes IgM, less IgG
Thermal range HDNB
4 - 37 Yes
Transfusion Reactions
Extravascular Intravascular

Yes Yes
ABO 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 antibodies

Non-red blood cell stimulated

ABO antibodies

Red blood cell stimulated

Antibodies formed as a result of transfusion, etc

Usually IgG

Active at 37C

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 Abs class Clinically Abs class

Significant IgM Significant IgM, IgG
No Yes
Thermal range HDNB Thermal range HDNB
4 - 15 No 4 - 37 Yes

Transfusion Reactions Transfusion Reactions

Extravascular Intravascular Extravascular Intravascular

No No Yes Yes