Bases moléculaires et relations structure-fonction des antigènes de groupe sanguin Duffy: récepteur de chimiokines et de Plasmodium vivax

Abstract

Duffy blood group antigens are of major interest in clinical medicine as they are not only involved in blood transfusion risks and occasionally in neonatal hemolytic disease, but also in the invasion of red blood cells by the hemoparasitic Plasmodium vivax. The FY locus maps to chromosome 1q22-q23, and is composed of 4 alleles: FY*A and FY*B (coding for the Fya and Fyb antigens, respectively), FY*X and FY*Fy. The Duffy antigens are carried by a 336 amino-acid glycoprotein named the Duffy Antigen/Receptor for Chemokines (DARC) that can bind with high affinity selected members of the CXC and CC classes of chemokines. Today, the genetic bases of the Duffy system have been characterized. The identification of the polymorphisms associated with the 4 alleles FY*A, FY*B, FY*Fy and FY*X has led to the development of a complete genotyping of the Duffy system by PCR, which increases the safety and lessens the risk of blood transfusion, and is useful in determining feto-maternal incompatibilities and in genetic filiation analyses. DARC is not solely expressed in erythroid cells: the same polypeptide isoform is found on the surface of endothelial cells of post-capillary venules throughout the body and also on the surface of Purkinje cells in the cerebellum, although it is encoded by different RNA messengers in each case, i.e., 1.35 and 7.5 kb, respectively. The preliminary analyses of receptor-ligand interaction have shown the existence of a chemokine-binding pocket defined by the close proximity of the first and fourth transmembrane domains of the DARC protein, and also by the importance of the N-terminal extracellular region for the binding of Plasmodium vivax merozoites.