THE ABO BLOOD GROUP SYSTEM
 Karl Landsteiner (1901;A,B,O)
 Adriano Sturli and Alfred von Decastello
(1902,AB)
 ABO antibodies are “naturally occurring”
and are initiated at birth, but are too low for
detection until individual is 3-6 months of
age
 Antibody production peaks at 5 and 10
years of age then declines later
General Characteristics
 ABO antibodies are IgM in nature
 ABO antibodies react preferentially at room
temperature (20-24C) or below and
efficiently activate complement at 37C
 Serum from Group O individuals contain
not only anti A and anti B but also anti-
AB
 Anti-A,B is not a combination of anti-A and
anti-B but a separate “cross reaction”
antibody of IgG nature
 Knowing the amount of Anti-A,B antibodies
in a woman’s serum or baby’s cord blood
can sometimes allow prediction or diagnosis
of HDFN
ABO grouping
 Forward typing (front type) – defined as
using known sources of commercial
antisera (anti-A, anti-B) to detect antigens
on a individuals RBCs
 Reverse typing (back type) – defined as
detecting ABO antibodies in the patient’s
serum by using known reagent RBCs
namely A and B cells
Formation of A,B,H and Red cell antigens
 ABH red cell antigens result from the
interaction of genes at 3 separate loci
(ABO,Hh and Se)
 Genes code for specific
glycosyltransferases
 A,B and H antigens can be glycolipid,
glycoproteins or glycosphingolipids and are
formed from the same basic precursor
material (paraglobloside or glycan)
Formation of A and B red cell antigens
 The H gene must be inherited to form ABO
antigens on the RBCs
 ABO antigens can be found on the surface
of RBCs as well as in secretions
 The Se gene must be inherited to form the
ABO antigens in secretions
 H and Se genes are closely linked and
located on chromosome 19 while ABO
genes are found on chromosome 9
Formation of A,B,H red cell antigens
 The H (HH or Hh) gene code for the
enzyme L-fucosyltransferase
 This enzyme attaches a fucose sugar to the
paragloboside structure forming the H
antigen
 H antigen is the precursor structure on
which A & B antigens are made
 Paragloboside chains
- Type 1&3 associated with body
secretions
- Type2&4 associated with red cell
membrane
 Most abundant types of precursor
structures on RBCs:
- Type 1 chain – precursor structure in
secretions
- Type 2 chain – precursor structure on
erythrocytes
Type of Precursor chains
 Type 1 precursor chain – refers to beta 1
 3 linkage between galactose and N-
acetylglucosamine
 Type 2 precursor chain – refers to beta 1
 4 linkage between galactose and N-
acetylglucosamine
 Expression of A and B antigens on RBCs
fully develop by 2-4 years of age and
remains constant
 RBCs of newborns estimated to carry about
25%-50% of the number of antigens sites
found on the adult RBC
Formation of the A Antigen
  The A gene (AA or AO) codes for the
production of a-3-N
acetylgalactosaminyltransferase which
transfers a N-acetylgalactosamine
(GalNac) sugar to the H antigen structure
 A gene tends to elicit higher
concentrations of transferase than B
gene leading to conversion of practically
all H antigens (a many as 810,000 to
1,170,000 antigen sites exit)
Formation of the B Antigen
 The B gene (BB or BO) codes for the
production of a-3-D-
galactosyltransferase which attaches
D-galactose (Gal) sugar to the H
substance on a type 2 precursor chain
 D-galactose confers group B specificity
(610,00-830,000 B antigen sites) on an
adult B RBC
Formation of AB Antigen
 When both A and B genes are inherited, the
B enzyme (a-3-D-galactosyltransferase)
competes more efficiently for the H
antigen > A enzyme (a-3-N-
acetylgalactosaminyltransferase)
 Average number of A antigens on AB adult
cell: 600,000 sites
 Average number of B antigens on AB adult
cell: 720,000 sites
Formation of O Antigen
 Blood group O individuals inherit at least
one H gene ( genotype HH or Hh) and
two O genes (OO)
 The H gene elicits the production of an
enzyme call a-2-L-fucosyltransferase
which transfers the sugar L-fucose to an
oligosaccharide chain on the terminal
galactose of type 2 chains
 O gene dose not elicit production of a
glycosyltransferase therefore, H
antigens remain unmodified
 L-fucose – a sugar responsible for the H
specificity
Formation of A,B, H Soluble Antigens
 ABH-soluble antigens (substances) can
be found in all body secretions and are
made up of glycoproteins
 Their presence is dependent on the
inheritance of the SeSe or Sese (secretor
gene) which codes for a-2-L
fucosyltransferase
 This enzyme modifies the type1 precursor
substance to form H substance which
determines a secretor
 People who inherit the sese genotype are
nonsecretors
ABO subgroups
 ABO subgroups represent phenotypes that
show weaker variable serologic reactivity
with the commonly used human antisera
anti-A, anti-B, anti-A,B reagents
- A subgroups
- Weak A subgroups
- Weak B subgroups
A subgroups
 Two different A antigens described by Emil
von Dungern in 1911 based on serologic
reactions
 More common than B subgroups
 A1: cells of approximately 80% of group A
(or AB)
 A2 or weaker A subgroups: remaining
20%
 Production of antigens is a result of the
inheritance of either A1 gene (more potent)
or A2 gene that codes for A transferase
 The immunodominant sugar is still N-
acetylgalactosamine
Characteristics of A1 and A2 Phenotypes
 About 1%-8% of A2 and 22%-35% of A2B
individuals produce anti-A1 (IgM) in their
serum
 Lectins used in blood banking:
- Dolichos biflorus (anti-Aq lectin) –
agglutinates A1 or A1B
- Bandeiraea simplicifolia (anti-B
lectin) – agglutinates B cells
 - Ulex europaeus (anti-H) – agglutinate
O cells ( H specificity) and other ABO
blood groups depending on the amount
of H antigen available

Blood Subgroup Anti-A reagent Anti-A1 lectin

(anti-A + anti reagent
A1)
A1 + +
A2 - 0

H Antigen

 Anti-H – a naturally occurring IgM cold

agglutinin occasionally found in the serum
of A1 and A1B individuals due to well-
hidden H antigen on their RBCs
 Insignificant antibody in terms of
transfusion because of no reactivity at body
temperature (37C)
 Anti-H lectin reacts weakly with the RBCs of
A1B individuals
O> A2 > B > A2B > A1 > A1B
Greatest amount of H Ag Least amount of H Ag

Theory of ABO subgroup

 Identification of 4 different forms/chains of H

antigens which corresponds to precursor
structures on which A enzyme can act to
convert to A antigen:
- Unbranched straight chains (H1 and
H2) – converted by A1 and A2 (less
efficiently) into Aa and Ab antigens
- Complex branched chains (H3 and
H4) – converted by A1 and A2 (very
poorly) into Ac and Ad
 A2 individuals with more unconverted
complex branched chains develop anti-
A1
 Infants appear as A2 at birth due to
deficiency of H3 and H4. Later developing
into A1 individuals in a few months.