HEM 2133
Immunohaematology IImmunohaematology I
Lesson 4: Isoantibodies of ABO
System
Blood Group Antigens
Made of glycoprotein and glycolipid molecules
on surface of RBC
Normal part of RBC plasma membrane
E.g. Person with blood group A will have E.g. Person with blood group A will have
antigen A on RBC plasma membrane
Genetically determined (i.e. inherited from
mother and father)
Antigens of ABO system
Each individual inherits one ABO gene from
each parent
These two genes determine which Ags are
present on RBC membranepresent on RBC membrane
One position or locus on each chromosome
number nine is occupied by an A, B or an O
gene
A locus termed H and the final product of the
genes at that locus, H antigen, is necessary for
the expression of normal ABO antigens
The ABO genes do not code for the production
of ABO antigens, but rather produce specific
glycosyl transferases
Glycosyl transferases add sugars to a basic
precursor substance on the RBCs
The inheritance of at least one H gene (HH or The inheritance of at least one H gene (HH or
Hh) obtain the production of an enzyme called
-2-L-Fucosyl transferase, which transfers the
sugar to the terminal galactose of the
precursor chain
The H substance must be formed for the other
sugars to be attached in response to an
inherited A and/or B genes
ABO Genetics
Genes at three separate loci control the
occurrence and location of A and B antigens
1. Hh genes H and h alleles
H allele codes for a fucosyltransferase H allele codes for a fucosyltransferase
enzyme that adds a fucose on precursor
substance to form the H antigen onto which
A and B antigens are built on red blood cells
h allele is a silent allele (amorph)
2. Se genes Se and se alleles
Se allele codes for a fucosyltransferase
enzyme that adds fucose to precursor
substance in secretory glands
Controls expression of H antigens in secretions
(i.e. saliva, body fluids, etc)(i.e. saliva, body fluids, etc)
se allele is an amorph
Secretor gene controls only the presence or
absence of the H substance in body secretions
It does not affect the presence of the H
substance on erythrocytes
3. ABO genes A, B and O alleles
A and B alleles code for glycosyltransferase (a
fucosyltransferase enzyme that add a sugar
onto H antigens to produce A and B antigens)onto H antigens to produce A and B antigens)
O allele does not code a functional enzyme
Hh gene H and h alleles
(h is an amorph)
Controls presence of H, A
and B antigens on both
RBCs and in secretions
Se gene Se and se
alleles (se is an amorph)
Controls presence of H
antigen in the secretionsalleles (se is an amorph) antigen in the secretions
ABO genes A, B and O
alleles
Inherit 1 gene from each
parent that codes for an
enzyme that adds a sugar
to the H antigen
H Antigen
The H gene codes for an enzyme
(fucosyltransferase) that adds a fucose to the
terminal sugar of a precursor substance
H antigen is the foundation upon which A and H antigen is the foundation upon which A and
B antigens are built
A and B genes code for enzymes that add an
immunodominant sugar to the H antigen
Formation of the A Antigen
The A gene codes for an enzyme that adds
GalNAc (N-Acetyl-D-galactosamine) to the
terminal sugar of the H Antigen
Formation of the B Antigen
B gene codes for an enzyme that adds D-
Galactose to the terminal sugar of the H
antigen
The H antigen is found on the RBCs when
there is an Hh or HH genotypes but not with
the hh genotype
The A antigen is found on the RBCs when The A antigen is found on the RBCs when
there is Hh, HH and A/A, A/O or A/B
genotypes
The B antigen is found on the RBCs when
there is Hh, HH and B/B, B/O or A/B genotypes
Amount of H Antigen According to
Blood Group
Blood group O people have red blood cells rich
in H antigen
Neither the A or B genes have converted the H
antigens to A or B antigens just a whole antigens to A or B antigens just a whole
bunch of H
Amount of H antigen
O > A2 > B > A2B > A1 >A1B
Subgroups of ABO
Subgroups differ in the amount of antigen
expressed on the red cell membrane (e.g. A1
red cells express about 5 times more A antigen
than A2 red cells)
Some subgroups highly branched, complex Some subgroups highly branched, complex
antigenic structures
Some subgroups simplified linear antigenic
structures
Most common subgroups A
Subgroups of A
A1 and A2
20% of group A and AB person belong to
subgroup A2 and 80% to A1 (both types of red
cells react with anti-A)
A failure to classify a weak subgroup of A may A failure to classify a weak subgroup of A may
lead the donor to be classified as a group O
and to be transfused to a group O patient
All group O donors must be tested with anti-A,
B to confirm that they are not actually weak
subgroups of A
Other ABO Subgroups
The other weaker subgroups of A exist
(extremely rare) : A3, Aint, Am, Ax, Ael
Subgroups of B even rarer
Bombay Phenotype
Normal people inherit a pair of H genes at a
locus separate from the ABO locus
The classic Bombay phenotype would be
expected to arise most frequently in the expected to arise most frequently in the
children resulting from consanguineous
marriages
Results in inheritance of an h gene from both
parents at the H locus
Unable to produce the H glycosyltransferase
Unable to produce H antigen
Regardless of the A, B or O genes inherited by
the individual , no A, B or H antigen is formed the individual , no A, B or H antigen is formed
In a homozygous hh individual, even if ABO
genes are present, the precursor for the
synthesis of these antigens is not produced in
the absence of H gene
This rare blood group is called Bombay group
(Oh)
Typed as group O persons with anti-A and
anti-B sera
Only anti-H can detect the Bombay blood Only anti-H can detect the Bombay blood
group
(other groups will give a positive reaction with
anti-H serum, the Bombay group will give a
negative reaction)
Antibodies of ABO system
Anti-A
Arises in sera of group B people
Will agglutinate the RBCs of all group A and
AB peopleAB people
Most of the anti-A is IgM, although small
amount of IgG and IgA may be present
Anti-A can functionally split into anti-A1, which
react with A1cells but not with A2cells
A1 antigen is more branched and therefore
reacts differently with anti-A than the less-
branched A2 antigen
A reagent made from the plant Dolichos A reagent made from the plant Dolichos
biflorus (lectin) can easily differentiate
between A1 and A2 cells
Anti-B
Serum from group A people contains an
antibody that agglutinates essentially all
group B and group AB RBCsgroup B and group AB RBCs
This antibody also readily agglutinates cells
suspended in saline, activates complement
and may rapidly destroy incompatible RBCs by
intravascular hemolysis
Anti-A, B
Found in sera of all group O people
Used to confirm group O donors and aid in
identification of weak subgroups of A and B
Anti-H Anti-H
May be found as a weak, cold-reacting antibody
in the sera of group A1 and A1B people
Found in the sera of people expressing the
Bombay phenotype
When tested with anti-H or U. europaeus lectin,
the RBCs of the Bombay phenotype are negative
Universal Donor
Group O
The red blood cells lack both A and B antigens
Group O donor red cells can be used in times
of urgency or emergency release of donor of urgency or emergency release of donor
units
Universal Recipient
Group AB
Lacks circulating ABO antibodies in plasma
May receive transfusion of RBCs from any ABO
phenotypephenotype
Beware: other antibodies may be present
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