Fy(a)/Fy(b) antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria

Autor(es):Mostrar menos -

King, Christopher L. ^{[1, 2]} ; Adams, John H. ^[3] ; Xianli, Jia ^[4] ; Grimberg, Brian T. ^[4] ; McHenry, Amy M. ^[3] ; Greenberg, Lior J. ^[4] ; Siddiqui, Asim ^[4] ; Howes, Rosalind E. ^[5] ; da Silva-Nunes, Monica ^[6] ; Ferreira, Marcelo U. ^[6] ; Zimmerman, Peter A. ^[4]

Afiliação do(s) autor(es)

^[1] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 - USA

^[2] Vet Affairs Med Ctr, Cleveland, OH 44106 - USA

^[3] Univ S Florida, Coll Publ Hlth, Tampa, FL 33612 - USA

^[4] Jia Xianli, Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 - USA

^[5] Univ Oxford, Dept Zool, Oxford OX1 2JD - England

^[6] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 108, n. 50, p. 20113-20118, DEC 13 2011.
• Citações Web of Science: 58

Resumo

Plasmodium vivax (Pv) is a major cause of human malaria and is increasing in public health importance compared with falciparum malaria. Pv is unique among human malarias in that invasion of erythrocytes is almost solely dependent on the red cell's surface receptor, known as the Duffy blood-group antigen (Fy). Fy is an important minor blood-group antigen that has two immunologically distinct alleles, referred to as Fy(a) or Fy(b), resulting from a single-point mutation. This mutation occurs within the binding domain of the parasite's red cell invasion ligand. Whether this polymorphism affects susceptibility to clinical vivax malaria is unknown. Here we show that Fy(a), compared with Fy(b), significantly diminishes binding of Pv Duffy binding protein (PvDBP) at the erythrocyte surface, and is associated with a reduced risk of clinical Pv in humans. Erythrocytes expressing Fy(a) had 41-50% lower binding compared with Fy(b) cells and showed an increased ability of naturally occurring or artificially induced antibodies to block binding of PvDBP to their surface. Individuals with the Fy(a+b-) phenotype demonstrated a 30-80% reduced risk of clinical vivax, but not falciparum malaria in a prospective cohort study in the Brazilian Amazon. The Fy(a+b-) phenotype, predominant in Southeast Asian and many American populations, would confer a selective advantage against vivax malaria. Our results also suggest that efficacy of a PvDBP-based vaccine may differ among populations with different Fy phenotypes. (AU)

• Processo FAPESP: 05/51988-0 - Epidemiologia da malaria: fatores de risco, distribuicao espaco-temporal e resposta ao tratamento em uma coorte rural amazonica.
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 03/09719-6 - Aquisicao de imunidade contra plasmodium vivax: estudo longitudinal em uma comunidade rural da amazonia brasileira.
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular