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Rh blood group antigens: from antenatal diagnosis of haemolytic disease of the new born to ammonium transport function Volume 10, issue 5, Septembre-octobre 2004

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Authors
Inserm U76, Institut national de la transfusion Sanguine, 6, rue Alexandre-Cabanel, 75015 Paris

The RH (Rhesus) system is one of the most immunogenic and polymorphic blood group system in human. Molecular basis of most Rh phenotypes, including the Rh null phenotype associated with hemolytic anemia of varying severity, have been now determined. The demonstration that the RH locus from RhD-positive individuals is composed of the RHD and RHCE genes, whereas the RHD gene is deleted in most RhD-negative individuals, allowed fetal RhD genotyping by invasive (DNA from amniotic cells) and non-invasive (fetal DNA from maternal plasma) PCR assays for antenal diagnosis of pregnancy at risk for Rh hemolytic disease of the newborn. Rh proteins (D and/or CcEe) carry Rh antigens and are only expressed on the erythrocyte surface in association with other membrane proteins {(RhAG (Rh associated glycoprotein), LW (ICAM-4), CD47 (IAP) and GPB)}. This Rh complex is also associated with the anion exchanger AE1 (Band 3). By interacting with protein 4.2 and ankyrin, two members of the spectrin-based skeleton, the Rh complex contribute in the maintenance of the stability and mecanical properties of the erythrocyte membrane. Hence, primary defects in Rh, RhAG, ankyrin or protein 4.2 are all associated with typical or atypical hereditary spherocytosis. In mammals, beyond the two erythroid Rh and RhAG proteins, the Rh protein family is composed of two non erythroid members, RhBG and RhCG, mainly expressed in liver and kidney, two major organs specialized in ammonia genesis and excretion. Functional analyses in heterologous expression systems or in human and murine red cells revealed that RhAG, RhBG and RhCG can mediate ammonium (NH 3 and/or NH 4 +) transport across the cell membrane and thus should represent the first specific ammonium transporter identified in mammals. Their physiological role in the regulation of the acid-base balance remained to be demonstrated. All these results identify proteins of the Rh family as new potential key structural and functional components of the plasma membrane from erythroid and epithelial cells.