ABO Blood Group System

Alaa Ibrahim Mohammed Hassan

Lecturer of Haematology &
Immunohaematology
FMLS, U of K
Objectives:
 On completion of this lecture, the student should be able
to:
• Classify the blood groups.
• Describe the relationship between ABO Ags and Abs for
the ABO blood groups O, A, B, and AB.
• Describe the general characteristics of ABO Ags.
• Predict the ABO phenotype & genotypes.
• Identify the frequencies of ABO blood groups in the
whites & blacks.
• Describe the formation of H, A, and B antigens on the
RBCs.
Blood Group systems:

 The blood groups are antigens that present on the

surface of RBCs.
There are more than 400 red blood cell antigens which

are grouped into many blood group systems.

 Blood group systems are classified according to their
clinical importance into two types:

1- Major blood group systems:

 Have a major clinical significance. Include:
 ABO blood group system.
 Rhesus blood group system.

2- Minor blood group systems:

 Have a minor clinical significance. This include:
 Duffy blood group system.
 Kell blood group system.
 Lewis Blood group system …etc
The clinical importance of blood group systems is

based on:
the frequency of the production of Abs.

 and the possibility to destroy the cells in vivo.

 ABO Blood Group System
(ABH Blood Group System)

The ABO system was the first to be recognized in

1901 and remain the most important blood group

system.
It was been discovered in 1901 by Karl Landsteiners.

He recognized 4 separate groups, named according

to the Ag present on the RBCs.

 Landsteiner observed that RBCs of some
individuals were agglutinated by the serum of
other individuals.
 He demonstrated that these people could be
classified into four groups according to which of
antigens were detectable: A, B, AB, and O.
 He also showed that an individual possesses
antibodiesAntigen
against the antigen
on RBCs
that he lack on his
Antibody in the serum
RBCs.
A Anti-B
B Anti-A
AB None
O Anti-A+B
 ABO Blood Groups

 Bloo
 Antigen
d
s on  Antibodies in Serum
Gro
RBCs
up

A A
 Anti-
B
B B  Anti-A
 AB  A and B  Neither
O  Neither  Anti-A and anti-B
 Landsteiners Rule

Landsteiners Rule:
(( If an antigen (Ag) is present on an
individual RBCs the corresponding
antibody (Ab) will NOT be present in the
individual plasma )).
General characteristics of the ABO antigens:
1. ABO antigens are widely distributed, located on RBCs,
lymphocytes, platelets, tissue cells, bone marrow and organs
such as kidneys.
ABO Ags are found on RBCs and all body
cells

2. Soluble forms of ABO sys. Ags can also be secreted by tissue

cells and can be detected in all body fluids except CSF.
3. ABO Ags which found on RBCs exist as either:
I. Glycoprotein, or
II. Glycolipid
4. Soluble forms are primary glycoproteins in nature.
 • Insoluble form of ABO Ags on RBCs are:
glycoprotein or glycolipid.
•Soluble form of ABO Ags in secretions are:
glycopreotein.

5. ABO Ags are detectable as early as 5-6 weeks in

utero (fetus blood).
6. Newborn have lower number of Ags copies per RBCs
and lake fully developed Ags structure than adults.
7. The full expression of adult levels of ABO Ags is
reached at approximately (2-4) years of age.
•ABO Ags:
-Detectable: 5 -7 weeks.
- Fully developed like adult level: 2 – 4 years.
Frequency of ABO phenotypes:
ABO Blood % in White % in Blacks
Group
A 40 27

B 11 20

AB 4 4

O 45 49
Inheritance & development of ABO (ABH) b. groups:
The occurrence and location of ABO Ags are
influenced by three genetically independent
loci:
1. ABO gene 2. H gene 3. Se
gene
 These loci determine:
The type of ABO Ags either A, B, AB or O
Ags.
Whether the individual is secretor or not
(soluble Ags in secretions).
a. Inheritance: Genotype & Phenotype:
Two genes inherited, one from each parent.
Individual who is A or B may be
homozygous or heterozygous for the antigen.
Heterozygous: AO or BO
Homozygous: AA or BB
Phenotype is the actual expression of the
genotype, i.e. group A
Genotype are the actual inherited genes
which can only be determined by family
studies, i.e.AO.
Example of Determining Genotype
Mom’s phenotype is group A, genotype AO
Dad’s phenotype is group B, genotype BO

B O
A AB 25% AO 25% (Group A)
O BO 25% (Group B) OO 25% (Group O)
Other Examples:

Mom Dad Offspring Blood

Group
AA BB 100% AB

BO OO 50% each of B
or O
OO OO 100% O

OO AO 50% each of A
or O
b. Development of ABO antigens:
The products of these genes are
enzymes. (transferases).
The ABO Ags are formed on a common
CHO structure called precursor substance
(PS).

So, our genes produce an specific

enzymes, these enzymes work on the
precursor substance in order to form the
ABO Ags.
ABO Genetics:

1. H gene 1. Controls presence of H, A,

and B antigens on both
RBCs and in Secretions

2. Controls presence of H
2. Se gene antigen in the secretions

3. Inherit 1 gene from each

parent that codes for an
3. ABO genes enzyme that adds a sugar to
the H antigen
Precursor substance
Precursor substance (PS):
 It is an oligosaccharide, with two types,
Type I: found in body fluids and secretions.
Type II: found on RBCs.

 These two types differ in their linkage & where they

have been found in the body.
 RBCs Ags are formed from the precursor substance
type II.
 The first Ag which is formed is the: H Ag.
 After that the A, B and O Ags are formed.
 Formation of H Ag:
The H gene is found on chromosome 19.

The H gene has two significant alleles: H and h.

The H allele is a dominant over the h allele.

• H/H or H/h phenotype: H, which will produce an enzyme.
• h/h phenotype: h, which have no enzyme product.

The gene product of H allele is an enzyme called

fucosyltransferase enzyme. (transfer a fucose suger).

The h allele is an a morphic (silent): has no product.

 Formation of H Ag:
- The H gene, which located on ch.19, from its H allele
produce an enzyme called L-fucosyltransferase enzyme
which transfer an L-fucose sugar into the terminal
galactose sugar of the precursor substance, so result in the
formation of H Ag.

H gene acts on
a Precursor
substance(PS)
by adding
Fucose sugar
The H Ag is also called H substance.

The formation of A & B Ags depends on the

formation of H Ag, while the formation of H Ag
DO NOT depend on ABO genes and ABO
formation
 Formation of A & B Ags:
The ABO gene is located on chromosome 9.
Three major alleles exist within the ABO locus: A, B, O.
A & B alleles are Co-dominant for each other
(both alleles will be expressed in heterozygous inheritance).
Genotype: A/A phenotype: A
Genotype: B/B phenotype: B
Genotype: A/B phenotype: A & B

While both A & B alleles are dominant over O allele

(They cover the O allele in heterozygous inheritance)
Genotype: A/0 phenotype: A
Genotype: B/0 phenotype: B
The gene product of A & B alleles is transferase
enzymes:
• A allele produce: N- acetyl-D-
galactosaminyltransferase.
• B allele produce: D-galactosyltransferse.

The gene product of O allele is called a silent or a

morph gene, considered as non functioning gene, which
produces an enzyme but with no catalytic activity.
 Formation of A Ag:
- The A allele, which located on ch.9, produces an
enzyme called N- acetyl-D-galactosaminyltransferase,.
which transfer an N- acetyl-D-galactosamine sugar
into the terminal galactose sugar of the H substance or
H Ag, so result in the formation of A Ag.

A gene acts on
the H substance
or H Ag by
adding
N- acetyl-D-
galactosamine
sugar
Formation of B Ag:
- The B allele, which located on ch.9, produces an enzyme
called D-galactosyltransferase,. which transfer a D-
galactose sugar into the terminal galactose sugar of the H
substance or H Ag, so result in the formation of B Ag.

B gene acts on
the H substance
or H Ag by
adding
D-galactose
sugar
So, the difference between A & B Ags is?
1. The type of enzyme produced from A & B
alleles.
2. The type of sugar which is transferred into the H
substance or H Ag.
Formation of A & B Ag:
 Because A & B genes are Co-dominant genes in
heterozygous inheritance; both genes will express a
transferase enzymes.
 So an individual of A/B genotype will produce the both
enzymes of A & B gene (N- acetyl-D-
galactosaminyltransferase and D-galactosyltransferse),
and each enzyme will convert the H substance or H Ag
into A Ags & B Ags respectively.
 Formation of O Ag:
- The O allele, which located on ch.9, is an produces
an inactive transferase enzyme, that have no
catalytic activity, so the H substance or H Ag
persist unchanged, as so phenotyped as group O.

The RBCs of
group O
individuals
have only an H
substance or H
Ags on its
surface.
ABO Genetics

1. Hh gene – H and h 1. Controls presence of H,

alleles (h is an a morph) A, and B antigens on
both RBCs and in
Secretions

2. Se gene – Se and se 2. Controls presence of H

alleles (se is an amorph) antigen in the secretions

3. ABO genes– A, B and O 3. Inherit 1 gene from each

alleles parent that codes for an
enzyme that adds a
sugar to the H antigen
The H substance or antigen

The A antigen

The B antigen
Notes:
The ABO genes do not code for the production of
ABO antigens, BUT rather produce specific
glycosyl transferases enzyme.

These glycosyl transferases add sugars

(Immunodominant sugar)to a common precursor
substance (PS )on the RBCs that firstly turned to H
substance by H gene .
 Immundominant Sugars responsible for H, A, and B Ags:

Immunodominant Glcosyltransferase
Antigen
sugar enzyme
Gene

H L-fucose L- fucosyl trnsferas H

N-acetyl-D- N acetylgalactosaminyl
A
galactoseamine transferase A

D- galactosyl
B D-galactose
transferase B
Bombay phenotype (Oh):
 It is a rare phenotype found in individuals who lack the H gene (hh

genotype).
 Bombay individual can not produce A or B Ags EVEN when

normal A and/or B genes have been inherited.

 Sera from normal group O contain only Anti-A and Anti-B, while

sera from bombay individuals contain Anti-A, Anti-B, and Anti-H.

 Therefore Bombay individual appear to be group O but also fail to

react with commercial anti H.

Thanks…
Next lecture enshallah, will be about:
 ABO antibodies.
 A subgroups.
Helpful Definitions:
 Glycosyltransferases: are enzyme that
facilitate the transfer of carbohydrate (sugar)
molecules onto carbohydrate precursor molecules

 Immunodominant sugar: is the sugar molecule

that complete the antigenic determinant when
combined with the precursor substance
 Genotype: The actual genetic makeup of the

individual for specific character.

 Phenotype: The detectable products that

produced by specific gene.

 Allele: Alternative gene that occupying same locus

or closely linked loci on the chromosome.

 Dominant genes: Genes that are expressed in the

heterozygous state in the absences or presents of other gene.

 Co-dominant gene: Two different gene that equally

expressed. The most of the blood group gene are co-

dominant.
 Amorphic gene: gene that fail to expressed it self whether

in heterozygous or homozygous state.

 Part – 2
A sub group & ABO antibodies
Subgroup of A :
The ABO phenotypes can be divided into categories
or subgroups.

In 1911; Van Dungern and Hirszfeld describe two

different types of A Ag known as:
A₁ and A₂ Ags .
These subgroups differ in the:
 amount of Ags expressed on the RBCs
membrane, representing quantitative difference
in Ags expression,
 qualitative difference in Ags expression.
ALL anti-A produced by group B individuals
contains two anti-A antibodies, namely:
anti-A and anti- A₁.
 Anti-A agglutinates cells of the groups A₁ , A₂ ,
A₁B and A₂B.
 But anti-A₁ agglutinates only the cells of group A₁
and A₁B.
(Anti- A₁ lectin):
 A₁ and A₂ RBCs can be distinguished in serological
testing only with specific reagents such as Dolichos
bifloris Lectin, which react only with A₁ RBCs.

Other A blood group subtypes:

 Further weak subgroups of A are also found (Ax,
AL,..), which have less clinical significant.
ABO antibodies:
ABO antibodies are naturally occurring Abs of
IgM class.

The production of ABO Abs in infants does not

begin until about 4 months of age .# to determine
an infant’s ABO type from a cell group.
Anti-A and anti-B levels are highest between ages
of 5 and 10 years, then they decrease and
sometimes difficult to detect in elderly
individuals.

ABO Abs like other Abs, are found in the globin

fraction of plasma.

They can be demonstrated in other body fluids

which contain plasma globulins, such as lymph,
exudate and milk, but are not usually found in
tears, saliva, urine, CSF or amniotic fluid.
They have the following properties:
I. React maximally at 4◦C, but the thermal
range of activity include 37◦C.
II. Agglutinate cells suspended in saline.
III. Are absorbable .
IV. The agglutinated cells adhere very strongly
and agglutinates are difficult to break up.
Thank you for attention…