title: Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals.
abstract: The Duffy (FY) blood group antigens are carried by the DARC glycoprotein, a widely expressed chemokine receptor. The molecular basis of the Fya/Fyb and Fy(a-b-) polymorphisms has been clarified, but little is known about the Fyx antigen and the FY*X allele associated with weak expression of Fyb, Fy3, Fy5, and Fy6 antigens. We analyzed here the structure and expression of the FY gene in 4 Fy(a-bweak) individuals. As compared with Fy(a-b+) controls, the Fy(a-bweak) red blood cell membranes contained residual amount of DARC polypeptide and these cells were poorly bound by anti-Fy antibodies and chemokines. The FY gene from Fy(a-b+) and Fy(a-bweak) individuals differed by one substitution, C286T. The resulting Arg89Cys amino acid change reduced the binding of anti-Fy antibodies and chemokines to DARC transfectants. We concluded that the Fybweak donors carried the FY*X allele at the FY locus and that the Fyx antigen corresponds to highly reduced expression of a grossly normal Fyb polypeptide caused by the Arg89Cys substitution. Because FY is a single copy gene, this defect should also affect DARC expression in nonerythroid cells. Because the Fyx phenotype is not associated with apparent clinical consequences, we discussed these findings in the light of the putative roles of DARC in various tissues. Finally, we developed a Fyx DNA typing assay that should be useful for genetic studies and clinical transfusion medicine.
authors.affiliation: INSERM U76, Institut National de la Transfusion Sanguine, Paris, France; the Centre National de Référence sur les Groupes sanguins, Paris, France; the Centre Régional de Transfusion Sanguine, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Tournamille
authors.forename: C
authors.initials: C
authors.lastname: Le Van Kim
authors.forename: P
authors.initials: P
authors.lastname: Gane
authors.forename: P Y
authors.initials: PY
authors.lastname: Le Pennec
authors.forename: F
authors.initials: F
authors.lastname: Roubinet
authors.forename: J
authors.initials: J
authors.lastname: Babinet
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
authors.forename: Y
authors.initials: Y
authors.lastname: Colin
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D000953:Antigens, Protozoan; D001120:Arginine / Q000235:genetics*; D001788:Blood Grouping and Crossmatching; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003545:Cysteine / Q000235:genetics*; D004375:Duffy Blood-Group System / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007518:Isoantibodies / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000097:blood; D008969:Molecular Sequence Data; D009154:Mutation; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000097:blood; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D007518:Isoantibodies; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; C061962:anti-Fy(a) antibody; D001120:Arginine; D003545:Cysteine