The Structure and Function of the Rh Antigen Complex
Section snippets
Terminology
Rh terminology distinguishes the antigens, genes, and the proteins. The antigens are referred to by the letter designations, D, C, c, E, e, etc. The RH genes are designated by capital letters, with or without italics, and include erythroid RHD, RHCE, and RHAG, as well as the non-erythroid homologs expressed in other tissues, RHBG and RHCG. The different alleles of the RHCE gene are designated RHce, RHCe, and RHcE, according to which antigens they encode. The proteins are indicated as RhD, RhCE
RH Genes and Rh Proteins
Two genes (RHD and RHCE) in close proximity on chromosome 1 encode the erythrocyte Rh proteins, RhD and RhCE; one carries the D antigen, and the other carries CE antigens in various combinations (ce, Ce, cE, or CE) (Fig 1A).16, 17, 18, 19 The genes each have 10 exons, are 97% identical, and arose via gene duplication. RhD and RhCE proteins differ by 32 to 35 of 416 amino acids (Fig 1B, shown as circles on RhD). In contrast, most blood group antigens are encoded by single genes with alleles that
Variant RhCE Genes and SCD
Altered RHce genes are prevalent in blacks and persons of mixed ethnic backgrounds. Individuals with variant alleles type as e-positive, but they often make alloantibodies with e-like specificities. Many altered RHce genes have been characterized (Fig 2C). The amino acid changes they encode that differ from conventional RHce are shown, and most carry a tryptophan→ cysteine at amino acid position 16 (W16C) encoded in exon 1, as well as additional changes, primarily in exon 5. Individuals
RH Genotyping and Transfusion Management in SCD
Transfusion of patients with SCD is a significant challenge in clinical transfusion medicine. SCD may be the single disease for which transfusion therapy may increase in the next decade as a result of the Stroke Prevention Trial in Sickle Cell Anemia (STOP). STOP was halted before its scheduled closure because of the significant benefit of chronic RBC transfusion in reducing the risk of stroke.46 STOP II further confirmed the markedly lower risk of stroke in participants receiving blood
Rh Glycoproteins (RhAG, RhBG, RhCG)
The Rh blood group proteins are well known because of their importance in blood transfusion. However, the mammalian family of Rh proteins has expanded with the discovery of Rh-associated glycoprotein, RhAG, in erythrocytes, and the related proteins, RhBG and RhCG, in other tissues. Erythrocyte RhAG is not polymorphic, and while it is not associated with any blood group antigen, it is important for targeting RhCE and RhD to the membrane. Mutations in RHAG are responsible for loss of Rh antigen
Summary
The genetic basis of the Rh blood group proteins has been intensely investigated in the past decade, and the polymorphisms responsible for most of the antigens have now been determined. Presently, routine genomic testing for RH is hampered because of the large number of Rh polymorphisms, as more than 100 RHD and 42 RHCE gene variants are known,30 and additional variants are still being discovered. Currently, RH genetic testing is a powerful adjunct to serologic methods; it is used to determine
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