Approximately 30 human blood group systems have been recognized, the best known of which are the ABO, Rh (Rhesus), and MNsystems. The term “blood group” refers to a defined set of red blood cell antigens, or blood group substances, controlled by a genetic locus having a variable number of alleles (eg, A, B, and O in the ABO system). The term “blood type” refers to the antigenic phenotype, usually recognized by the use of appropriate antibodies.

The ABO System Is of Crucial Importance in Blood Transfusion The ABO system was discovered by Landsteiner in 1900 while investigating the basis of compatible and incompatible trans fusions in humans. The membranes of the erythrocytes of most individuals contain one blood group substance, either type A, B, AB, or O. Individuals of type A have anti-B anti bodies in their plasma that will agglutinate the erythrocytes in type B or type AB blood. Individuals of type B have anti-A antibodies that will agglutinate type A or type AB erythrocytes. Type AB blood has neither anti-A nor anti-B antibodies, and has been designated the universal recipient. Type O blood has neither A nor B antigens, and has been designated the universal donor. The above description has been simplified consider ably, as further subgroups exist such as A1 and A2 . The genes responsible for production of the ABO substances, which are located on the long arm of chromosome 9, fall into three genotypes, or alleles, two of which are codominant (A and B) and the third (O) recessive; these ultimately determine which of the four phenotypic products is synthesized: the A, B, AB, and O substances.

The ABO Antigens Are Glycosphingolipids & Glycoproteins

 The ABO antigens or, as they are sometimes referred to, sub stances consist of a set of complex oligosaccharides located on the surface of most cells and as a component of many secretions (Figure 1). In red blood cells, these antigens are generally anchored to the cell surface by covalent attachment to a membrane lipid, forming a type of molecule known as a glycolipid. In secretions the same oligosaccharides are anchored to proteins, formingglycoproteins. Their presence in secretions is determined by a gene designated Se (for secretor), which codes for a specific fucosyl (Fuc) transferase in secretory organs, such as the exocrine glands. This gene is normally silent in other cells. Individuals of SeSe or Sese genotypes secrete either or both A and B antigens whereas individuals of the sese genotype do not. However, red blood cells of both genotypes can express the A and B glycolipid antigens.

Fig1. Diagrammatic representation of the structures of the H, A, and B blood group substances. R represents a long complex oligosaccharide chain, joined either to ceramide where the substances are glycosphingolipids, or to the polypeptide backbone of a protein via a serine or threonine residue where the substances are glycoproteins. Note that the blood group substances are biantennary; that is, they have two arms, formed at a branch point (not indicated) between the GlcNAc—R, and only one arm of the branch is shown. Thus, the H, A, and B substances each contains two of their respective short oligosaccharide chains shown above. The AB substance contains one type A chain and one type B chain.

TheAGene Encodes a GalNAc Transferase, the B Gene a Gal Transferase, & the O Gene an Inactive Product

 H substance, the blood group substance found in persons of type O, is the precursor of both the A and B substances (see Figure 1). It is formed by the action of a fucosyl transferase, coded for by the H locus, that catalyzes the addition of an α1 → 2 linked fucose onto the terminal Gal residue of its precursor:

The A gene encodes a UDP-GalNAc-specific GalNAc transferase that adds a GalNAc to H substance, forming A substance. The B gene encodes a UDP-Gal-specific Gal transferase that adds the Gal residue to H substance to form B substance. Individuals of type AB possess both enzymes, and thus synthesize two oligosaccharide chains (see Figure 1), one with a terminal GalNAc and the other with a terminal Gal.

Anti-A antibodies recognize the additional GalNAc residue present in the A substance, and anti-B antibodies recognize the additional Gal residue found in the B substance. Type O individuals harbor a frameshift mutation in the gene encoding the terminal glycosyltransferase that results in the production of an inactive protein. Thus, H substance thus constitutes the O antigen.

An h allele arises when a mutation in the portion of H locus that codes for the fucosyltransferase yields an inactive enzyme. While individuals of the heterozygous Hh genotype still can synthesize adequate levels of H substance, hh homozygous individuals cannot. Since H substance is the precursor for A and B substances, all individuals carrying the hh genotype will have red blood cells of type O regardless of whether or not they express one of both of the A and B terminal glycosyltransferase(s). This is referred to as the Bombay phenotype (Oh).

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