ABO and RH Blood Groups

Prof. C.A. Nwauche

ABO antigens
 Introduction
 Landsteiner ; Decastello and Sturli, discovered the ABO system
in early 1900s.
 The ABO system was the first to be discovered and remains the
most important.
 Landsteiner’s Law: In order to explain the
agglutination patterns, Landsteiner postulated that
there were two antigens (A and B) and two antibodies
against those antigens (anti-A and anti-B)-He assumed
the presence of the antibodies in the sera of individuals
who did not express those antigens.
Introduction II

 Most persons >6 months have clinically significant Anti-A and/or anti-B in their serum, if
they lack the corresponding antigens on their red cells.
 In addition to the four major groups (A, B, AB, and O), we now know that additional
subgroups exist that exhibit different patterns and degrees of agglutination- using
reference RBCs and antibodies.
Introduction III

 These subgroups include A1, A2, etc.

 A2 cells react more weakly than A1 cells with anti-A.

 The natural antibodies seem to occur due to constant or occasional immunologic

stimulation by substances, such as food, pollen, and bacteria, that are ubiquitous in
nature.
 Nigeria (Nwauche et al):
 O-56.3 %; A-22.65%;B-19.02%;AB-2.10%.
Applications

 These antigens exist in cells other than RBCs, including white cells
and platelets.
 ABO matching is important not only in blood transfusion but also
in cell, tissue, and organ transplantation.
 Forensic science utilizes the ABO blood groups for suspect
exclusion in the analysis of crime scene evidence, such as blood,
saliva, seminal fluid, and even hair.
 Paternity Testing.
Paternity Testing
Blood group Exclusion criteria
Exclusion of a falsely accused father
 Ist order-a blood group gene cannot be detected in a child unless present in
one or other of both parents.

 2nd order-If one or other of a parent is homozygous for a particular blood group
gene, its product must appear in the blood of the child.

 A parent cannot pass on an antigen he/she does not

have
Structure of ABH Antigens

 In the 1950s,a group led by Watkins and Morgan and

another group led by Kabat played a major role in the final
determination of the chemical nature of ABH antigenicity.
 These studies revealed that the immunodominant
structures of those antigens are oligosaccharides.
 The ABH antigens occur on glycoproteins,
glycolipids, and as free oligosaccharides.
Biosynthetic Pathway of ABH Antigens.

 Because these structures are oligosaccharides and

cannot be the primary gene products of proteins, it
was assumed that they were synthesized by the
actions of enzymes encoded by the genes.

 A and B glycosyltransferases catalyze the final step

of biosynthesis of A and B oligosaccharide antigens.
Biosynthetic Pathway of ABH Antigens II

 Functional A and B alleles at the ABO locus encode A and B glycosyltransferases that
catalyze the addition of an N-acetyl-D-galactosamine and D-galactose by an alpha 1-3
glycosidic linkage to synthesize the A and B structures respectively.

 Experimental evidence showed that A transferase activity was observed in the tissues and
sera that exhibited A antigens whereas B transferase activity was detected in the tissues and
sera that exhibited B antigens.
Naturally occurring antibodies

 These are usually of the IgM variety, but occasionally Igg.

 They occur naturally to A and or B antigens.
 Found in the plasma of individuals that lack the corresponding antigens on their red cells.
The H Antigen

 The H antigen is the precursor upon which the products of the ABO genes act.
 It segregates independently from ABO.
 It is present on red cells.
 The gene is absent in the Bombay phenotype, such individuals are hh.
 The serum of Bombay subjects contains anti-H, anti-A and/or anti-B
Secretor Gene

 80% of the population possess the secretor gene.

 Here, the ABH antigens are found in soluble form in secretions and body fluids(e.g. saliva,
plasma, sweat, semen, etc).
Rh (Rhesus) antigens
Rh Proteins

 The antigens of the Rh blood group system are

located on two proteins.
 RhD carries the D (Rh1) antigen,and RhCE carries the C, c, E, and e
(Rh2 to Rh5) antigens.
 Both proteins are composed of 417 amino acids.
Rh Proteins

 The antigens of the Rh blood group system are

located on two proteins.
 RhD carries the D (Rh1) antigen,and RhCE carries the C, c, E, and e
(Rh2 to Rh5) antigens.
 Both proteins are composed of 417 amino acids.
Rh phenotype

 The Rh gene may be either present or absent.

 This produces the Rh D+ or Rh D-phenotype respectively.
Rh antibodies

 Rarely occur naturally.

 They are immune-produced in response to previous antigenic stimulation-previous
transfusions, pregnancy, abortions, etc.
 Anti-D is responsible for most of the clinical complications of the Rh blood group system.
 Clinical usage: Rh Dt and Rh D- groups of patients
Variability of the Rh gene locus

 Several different mechanisms contributed to the large number of RH alleles.

 Also shared by most other genes and contributes to the complexity of other blood groups, like the
Kell and Lutheran groups.
 Missense mutation: single nucleotide substitution cause changes of the encoded amino acid leading
to a single amino acid substitution.
 Nonsense mutation: Introduction of a premature stop codon leading to a truncated protein.
 Splice site mutation: Destruction of the splice consensus sequence preventing the correct splicing of
the allele.
 Frameshift: Insertions or deletions of one or a few nucleotides usually lead or resulting in
completely aberrant amino acid sequences.
 Recombinations: involving different alleles lead to alleles sharing peculiarities of both parent alleles.
Other blood group systems

 These include:
 Kell-warm, occassional cause haemolytic transfusion reaction(HTR), HDN.
 Kidd-warm, occasional cause of HTR, HDN
 Lutheran-react at low temperatures
 Duffy-warm temperatures
 Lewis-Low temperatures.
 MNS-Low temperature.
 P(Pl)-low temperature.