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Blood group antigens are structures on the outer surface of human red blood cells (RBCs) that can be recognized by the immune system of individuals who lack that particular structure. Identification of RBC antigens and antibodies is the basis of pretransfusion compatibility testing and the safe transfusion practices used today and provides insights into understanding the etiology of hemolytic disease of the fetus and the newborn. Biochemical and molecular studies have led to definition of the biologic functions of molecules expressing blood group antigens. These molecules play a critical role in susceptibility to infection by malarial parasites, some viruses, and bacteria. Alteration of RBC antigen expression is associated with many molecular backgrounds, and some play a role in the clinical manifestations of certain diseases. Erythrocytes, far from being inert containers of hemoglobin, are active in a variety of physiologic processes.

Acronyms and Abbreviations

AET, 2-aminoethylisothiouronium bromide; AQP1, aquaporin 1; AUG, antigens of the Augustine; CD, cluster of differentiation; DTT, dithiothreitol; EKLF, erythroid Krüppel-like factor; EDTA, ethylenediaminetetraacetic acid; Fuc, fucose; Gal, galactose; GalNac; GPA, glycophorin A; GPB, glycophorin B; GPC, glycophorin C; GPD, glycophorin D; GlcNAc, N-acetylglucosamine; GPI, glycosylphosphatidylinositol; HDFN, hemolytic disease of the fetus and newborn; HEMPAS, hereditary erythroblastic multinuclearity with a positive acidified serum test; Ig, immunoglobulin; ISBT, International Society of Blood Transfusion; LAD, leukocyte adhesion deficiency; 2-ME, 2-mercaptoethanol; NeuAc, N-acetylneuraminic acid; PNH, paroxysmal nocturnal hemoglobinuria; RBC, red blood cell.


A blood group system consists of a group of antigens encoded by alleles at a single gene locus or at gene loci so closely linked that crossing over does not occur or is very rare. An antigen collection consists of antigens that are phenotypically, biochemically, or genetically related, but the genes encoding them have not been identified.1 Placement of a blood group antigen into a system or collection begins with the discovery of an antibody, usually in the serum of a multiparous woman or a multiply-transfused recipient, with a unique pattern of reactivity. The antibody can be used to study basic biochemical properties of the corresponding antigen, to enable recognition of the pattern of inheritance of the antigen in families and in populations, to identify red blood cells (RBCs) that lack the antigen, and to search for an antithetical antigen. Identified characteristics, such as prevalence of positive reactions or sensitivity or resistance to specific enzymes, are compared with antigens in known systems and collections. A newly recognized antigen is also evaluated using biochemical and molecular genetic methods. Orphan antigens of low or high prevalence are placed in “holding tanks” until the gene that encodes them is established.

The majority of genes encoding blood group antigens have been cloned and sequenced,2 and the molecular bases of most blood group antigens have been determined.3–6 Details on the alleles associated with blood group antigens and phenotypes can be obtained from the International ...

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