Dr. Nawsherwan Sadiq Department of

Pathology/HaematologyHawler Medical University

College of Medicine

ABO SYSTEM• There are four main blood groups: A, B, AB and O. • In the British Caucasian population, the frequency

of group A is 42%, B 9%, AB 3%, and O 46% • there is racial variation in these frequencies.[6] The

epitopes of ABO antigens are determined by carbohydrates (sugars), which are linked either to polypeptides (forming glycoproteins) or to lipids (glycolipids).

In Caucasians the most frequent ABO phenotype is the O followed by A, B and least is AB.

Three genes on Chromosome 9 determine the ABO phenotype namely A, B and O gene.

• The A and B genes do not code for A or B antigens, but they code for specific enzymes “Glycosyl transferases” which add sugars to a basic precursor substance.

• The expression of the A and B antigens requires the presence of an independently inherited H gene.

• The immunodominant sugar added to produce the

• A antigen is : N-acetylgalactoseamine

• B antigen is : D-galactose

• H antigen is : L-Fucose.

Enzymes are:

• A antigen : α-3-N-acetylgalactosaminyl transferase.

• B Antigen :α-3-D-galactosyl transferase

• H antigen : α-2-L-fucosyl transferase.

Frequency of Blood Groups in the General Population

Blood Groups Frequency (%)

Type

O   47

A   41

B   9 

AB   3 

Rh factor

Rh  - 15

Rh  + 85

From Guyton AC: Textbook of Medical Physiology, 6th ed. Philadelphia, WB Saunders, 1981.

In the extremely rare Oh Bombay phenotype, the individual is homozygous for the h allele of FUT1 and hence cannot form the H precursor of the A and B antigen.

Their red cells type as group O, but their plasma contains anti-H, in addition to anti-A, anti-B, and anti-A,B, which are all active at 37°C.

As a consequence, individuals with an Oh Bombay phenotype can only be safely transfused with other Oh red cells

• Subjects with H Antigen should either be HH or Hh,

• if he/she is hh, then no L-Fucose is added, so no H, A or B antigens could be produced. called Bombay blood Group.

• The H gene is seen in 99.99% of subjects (either Hh, or HH),

• the hh is very rare seen in 0.01%.

• Two common subgroups of the A antigen. Approximately 20% of group A and group AB individuals belong to group A2 and group A2B.

• The remainder belonging to group A1 and group A1B.

• These subgroups arise as a result of inheritance of either the A1 or A2 alleles.

• A2 red cells have fewer A antigen sites than A1 cells and the plasma of group A2 and group A2B individuals may also contain anti-A1.

• The distinction between these subgroups can be made using the lectin Dolichos biflorus, which only reacts with A1 cells

• The H antigen content of red cells depends on the ABO group.

• The strength of reaction tends to be graded O > A2 > A2B > B > A1 > A1B.

• Other subgroups of A are occasionally found (e.g., A3, Ax) that result from mutant forms of the glycosyltransferases produced by the A gene

• A phenotype : the Genotype maybe either AA or AO.

• B phenotype : The Genotype maybe either BB or BO.

• AB phenotype : The Genotype is AB.

• O phenotype : The Genotype is OO.

• ABH antigens develop as early as 37 days fetal life.

Weakly expressed throughout fetal life.

• In newborn the ABO Ag sites are about 25-50% strength of those in adults.

• The number of antigen sites reaches “adult” level at around 1 year of age and remains constant until old age, when a slight reduction may occur..

Secretors and Nonsecretors • The ability to secrete A, B, and H substances in

water-soluble form is controlled by FUT2 (dominant allele Se).

• In a Caucasian population, about 80% are secretors (genotype SeSe or Sese) and 20% are nonsecretors (genotype sese).

• Secretors have H substance in the saliva and other body fluids together with A substances, B substances, or both, depending on their blood group.

• Only traces of these substances are present in the secretions of nonsecretors, although the antigens are expressed normally on their red cells and other tissues.

• An individual's secretor status can be determined by testing for ABH substance in saliva

ABO Antigens and Disease

• Group A individuals rarely may acquire a B antigen from a bacterial infection that results in the release of a deacetylase enzyme.

• This converts N-acetyl-D-galactosamine into α-galactosamine, which is similar to galactose, the immunodominant sugar of group B.

• Thereby sometimes causing the red cells to appear to be group AB.

• Case reports attest to the danger of individuals with an acquired B antigen being transfused with AB red cells, resulting in a fatal haemolytic transfusion reaction following the production of hyperimmune anti-B.

• Group A individuals have 1.2 times the risk of developing carcinoma of the stomach than group O or B;

• Group O individuals have 1.4 times more risk of developing peptic ulcer than non-group O individuals.

• Nonsecretors of ABH have 1.5 times the risk of developing peptic ulcer than secretors.

• The ABO group also affects plasma von Willebrand factor (vWF) and factor VIII levels; group O healthy individuals have levels around 25% lower than those of other ABO groups.

• ABH antigens are also frequently more weakly expressed on the red cells of persons with leukaemia.

• Regarding the ABO group, all normal healthy individuals consistently have present in their sera, antibodies to antigens they lack on their red cells.

• This is not true regarding other blood groups.

ABO Abs

• Naturally occurring• Bacteria, pollen seeds, diet, or other substances

present in nature have been implicated in stimulating Antibody development..

• Starts at first few months after birth.• Detectable titres of Abs by 3-6 months.• Peaks at 5-10 yrs.• Declines progressively with advanced age.• 0.01% healthy individuals may not have natural

occurring antibodies.

Rh SystemDECce

• Wiener Rh-Hr terminology shorthand designation: is among the most commonly used ones to denote Rh haplotype

• R1 CDe r cde

• R2 cDE r’ Cde

• Ro cDe r” cdE

• Rz CDE ry CdE

• In Caucasians :

R1 > r > R2 > Ro > r’ > r”.

• Rhnull is a person who expresses no Rh Antigens on his red cells (---/---)

Weak D or Du

• Maybe detected by some but not all anti-D reagents or by using IAGT and not directly.

• Most are IgG.

• React optimally at 37C.

• They have been significantly linked to Hemolytic disease of the newborn and hemolytic transfusion reactions.

• Immunogenecity of the RH Antigens in order of potency D>c>E>C>e.

Lewis

• Lewis antigens are not synthesized by the red cells

• Lewis Antigens are made up by tissue cells and secreted into the fluids and plasma.

• They are then absorbed onto the RBC membrane.

• Lewis antigens in secretions are glycoproteins, on cell membranes glycolipids.

• There antibodies are rarely reactive at 37 C, therefore they are not significant.

Kell System

• Found only on RBC

• Well developed at birth.

• It is next to D in immunogenecity.

• Anti-K is an immune IgG antibody detectable by IAGT .

• Anti-K is implicated in HDN and HTR.

Duffy blood group

• Fya and Fyb are well developed at birth .

• Fy (a-b-) prevalent in blacks and linked with resistance to malaria.

• Anti Fya and Fyb are IgG immune antibodies.

• They are reactive by IAGT.

• They are important causes of HDN and HTR.

KIDD System

• JkJkaa and Jk and Jkbb antigens are well developed at antigens are well developed at birth.birth.

• Anti JkAnti Jka a and Jkand Jkbb are immune IgG are immune IgG antibodies.antibodies.

• These antibodies unlike duffy’s are These antibodies unlike duffy’s are enhanced by enzymes.enhanced by enzymes.

• Common causes of severe delayed Common causes of severe delayed transfusion reactions and HDN.transfusion reactions and HDN.

Other Blood Group systemsOther Blood Group systems

• P system

• Lutheran.

• MNSs system.

• Ii system.

• Less important than those before mentioned.