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Hématologie

Molecular basis of RH blood groups and Rhnull deficiency syndrome Volume 3, numéro 3, Mai-Juin 1997

  • Auteur(s) : Jean-Pierre Cartron, Yves Colin
  • Mots-clés : blood groups, Rh antigens, D epitope mapping, red cell membrane, null phenotypes.
  • Page(s) : 207-20
  • Année de parution : 1997

The Rh blood group antigens are carried by a family of nonglycosylated hydrophobic transmembrane proteins of 30-32 kDa which are missing from the red cells of rare Rhnull individuals that exhibit several membrane defects. The Rh proteins (D and Cc/Ee, respectively) are encoded by two homologous genes RHD and RHCE (96 % sequence identity) tandemly organized on chromosome 1p34-p36, and which most likely derived by duplication of a common ancestral gene. The D and non-D proteins (417 amino acids) differ by 35 substitutions and exhibit a similar membrane topology with short hydrophilic loops connecting the twelve putative transmembrane helices. The molecular basis of the RH genes and proteins polymorphisms have been established by analysis of many common and rare variants. The presence or the absence of the RHD gene and of its product determined the basis of the Rh-positive and Rh-negative phenotypes, respectively, whereas amino acid polymorphisms at positions 103 and 226 of the RHCE gene product determined the molecular basis for the C/c (Ser Æ Pro) and E/e (Pro Æ Ala) specificities, respectively. Other polymorphisms occur by gene conversion between the two RH genes and by single point mutations. Comparative analysis of the immunological and molecular anomalies typical of partial D phenotypes (D-positive individuals that produce alloanti-D antibodies) provided a preliminary mapping of the D epitopes on the D polypyptide. Rhnull individuals suffer a clinical syndrome of varying severity and their red cells are characterized by abnormalities of the morphology, the function (cation transport) and the membrane phospholipid asymmetry. In addition to the Rh proteins, several other glycoproteins (Rh50, CD47, LW, GPB) are absent or severely decreased on these cells. These findings suggest that the Rh proteins are assembled by non covalent linkages into a complex with these glycoproteins. Molecular analysis indicate that most cases of Rh deficiency are caused by mutations within the gene encoding the Rh50 subunit. Further studies should clarify the trafficking, assembly and potential function of each component in this complex.

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