Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals.

Tournamille, C; Le Van Kim, C; Gane, P; Le Pennec, P Y; Roubinet, F; Babinet, J; Cartron, J P; Colin, Y

Tournamille, C; Le Van Kim, C; Gane, P; Le Pennec, P Y; Roubinet, F; Babinet, J; Cartron, J P; Colin, Y.

Afiliación

Tournamille C; 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.

Blood ; 92(6): 2147-56, 1998 Sep 15.

Article en En | MEDLINE | ID: mdl-9731074

RESUMEN

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.

Asunto(s)

Sustitución de Aminoácidos/genética; Antígenos de Protozoos; Arginina/genética; Proteínas Portadoras/biosíntesis; Cisteína/genética; Sistema del Grupo Sanguíneo Duffy/genética; Proteínas de la Membrana/biosíntesis; Proteínas Protozoarias; Receptores de Superficie Celular/biosíntesis; Receptores de Quimiocina/biosíntesis; Alelos; Animales; Tipificación y Pruebas Cruzadas Sanguíneas; Western Blotting; Células COS; Proteínas Portadoras/análisis; Proteínas Portadoras/genética; Sistema del Grupo Sanguíneo Duffy/biosíntesis; Humanos; Isoanticuerpos/metabolismo; Proteínas de la Membrana/sangre; Datos de Secuencia Molecular; Mutación; Receptores de Superficie Celular/análisis; Receptores de Superficie Celular/genética; Receptores de Quimiocina/sangre; Transcripción Genética; Transfección

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Proteínas Portadoras / Proteínas Protozoarias / Receptores de Superficie Celular / Receptores de Quimiocina / Sustitución de Aminoácidos / Cisteína / Sistema del Grupo Sanguíneo Duffy / Proteínas de la Membrana / Antígenos de Protozoos Límite: Animals / Humans Idioma: En Revista: Blood Año: 1998 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos

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