The ABO and Rh are the major (clinically significant) blood
group antigens though almost 400 of them have been
recognized. Given below are the more important blood
1. ABO, 2. Rhesus, 3. Dell, 4. Duffy, 5. Kidd, 6. Lutheran,
7. Lewis, 8. P, 9. MNS, 10. I. (All of the above if mismatched
can cause hemolytic transfusion reaction and 1 to 6 can be
responsible for hemolytic disease of the newborn).
Naturally Occurring Antibodies
Under normal circumstances, the newborn has no ABO
antibodies. However, after 10–20 weeks later, moderate
amount of antibodies are present which appear without any
specific antigenic stimulus. So, these are called naturally
occurring antibodies. Anti-A and anti-B are important
examples of this class. They are IgM immunoglobulins,
they react optimally at room temperature, they are also
called cold antibodies. They are complete antibodies in
serological behaviors, because these antibodies readily
agglutinate the red cells carrying the corresponding
Immune antibodies are produced in response to
immunization by either transfusion or pregnancy.
They are usually IgG antibodies, they react best at body
temperature—37°C and are called warm antibodies. Rh
antibody (anti-D) is important immune antibody. They are
often called incomplete antibodies as they do not cause
agglutination of red cells with corresponding antigen in
saline. These antibodies cause only sensitization or coating
In 1900, Karl Landsteiner discovered the blood
groups ABO and classified blood into A, B and O groups.
A fourth blood group ‘AB’ was discovered by Landsteiner’s
associates, Von Decastello and Struli in 1902.
The four blood groups are determined by the presence
or absence of blood group antigens (agglutinogens) on red
blood cells and accordingly an individual’s group is A, B,
AB or O (O denotes absence of A or B antigens). In addition,
it has been shown that corresponding to antigen A and
B, there are naturally occurring antibodies anti-A and
anti-B (agglutinins) in the plasma/serum of individuals
whose red cells lack the corresponding antigen. Group A
individuals have anti-B, group B individuals have anti-A,
group, O individuals have both anti-A and anti-B and group
AB individuals have no agglutinins in plasma/serum.
It was further shown that Group A could be subdivided
into two principal subgroups A1 and A2. On the basis of
this, ABO system is divided in six main groups A1, A2, B,
Genetics of ABO System (Table 11.1)
The ABO system follows Mendelian law of inheritance.
The locus for ABO grouping is a chromosome 9, which
is occupied by one of three major allelic genes namely,
A, B and O. Each individual has a pair of chromosomes
(one from each parent). The A and B genes are dominant,
while O gene is recessive, thus, not detected directly and
accordingly absence of A and B antigens on red cells
indicates ‘O’ blood group (Fig. 11.1).
TABLE 11.1: The ABO antigens and corresponding antibodies
Antigen on RBC Antibody in Plasma/serum Bloodgroup
318 Concise Book of Medical Laboratory Technology: Methods and Interpretations
The expression of A and B genes appears to be dependent
on another gene called H gene. H gene is inherited,
independent of A, B and O genes. H gene is expressed as
both homozygous (HH) and heterozygous (Hh). When
no H gene is inherited, a (hh) phenotype results which is
extremely rare. This is commonly called Bombay group.
Bombay group individuals are homozygous for hh gene.
As shown in Figure 11.2, there is a basic precursor
substance which is converted to H substance by an enzyme
L. Fucosyltransferase (a product of H gene).
H substance is next acted upon by A and/or B gene
specified transferase enzyme and is converted to A and/or
B antigens. The ‘O’ gene is an amorph (no gene product)
and thus, group ‘O’ cells enter only H substance.
The persons with genetic configuration of ‘hh’ cannot act
on the precursor substance and the precursor substance
remains unaltered. Since no H substance is produced, the
ABO genes remain inactive and there is no conversion to
A, B or H antigen (These are the persons called Bombay
Anti-A serum very seldom differentiates between A1 and
A2. For this reason, we use human anti-A1 and lectin anti-A
which agglutinate A1 and A1B cells but not A2 and A2B cells.
About 20% of persons with A antigen in A or AB group are
It is not necessary to classify group A patient or donors
as A1 or A2 except when the individual serum contains
anti-A1. Anti-A1 occurs in the serum of 1–8% of A2 group
persons and 22–35% of A2B group persons.
Anti-A1 causes discrepancies between ABO cell and
Subgroups weaker than A2 occur infrequently. They
are characterized by declining number of ‘A’ antigens on
red cells and reciprocal increase in H reactivity. Weaker
variants of A are A3, Ax, Am and A intermediate.
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