Polimorfismos de genes associados à resposta imune humoral em indivíduos naturalmente infectados pelo Plasmodium vivax no Estado do Pará

• Autor(a) principal: Cassiano, Gustavo Capatti [UNESP]
• Data de Publicação: 2014
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/122186
• topic: Genetica humana; Malaria - Aspectos genéticos - Pará; Polimorfismo (Genetica); Plasmodium vivax - Pará; Imunogenetica; Human genetics

Malaria is one of the main causes of morbidity and mortality in the tropics and subtropics areas of the world. Although the immunity is only partial, it is important in reducing the amount of illness and death caused by malaria. However, the immunity against malaria is complex, and one of the main goals of vaccine developers is to understand why people differ in their immune response to the parasite. The present research aims to investigate the genetic mechanisms related to humoral immune response against P. vivax blood stages antigens, predominant malaria species in Brazil. Nine single nucleotide polymorphisms (SNPs) in 7 genes (CD28, CTLA4, ICOS, CD86, CD40, CD40L e BLYS) were determined by PCR-RFLP. A total of unrelated 227 individuals infected with P. vivax from the Goianésia do Pará, Pará state, participated in this study. Level and prevalence of IgG antibodies against N-terminal (ICB2-5) and C-terminal (MSP-119) regions of MSP-1, DBP and AMA-1 of P. vivax were measured by ELISA. First, we evaluate the influence of genomic ancestry on distributions of co-stimulatory genes polymorphisms in an admixed Brazilian population using ancestry informative markers. ICOS, CD40L and CD86 polymorphisms were associated with genomic ancestry. There were significant association between CD28 -372G>A, ICOS +1564T>C, and CD40L -726T>C SNPs with antibodies anti-DBP prevalence. Moreover, CD40 -1C>T and CD86 +1057G>A SNPs were associated with antibody levels anti-PvMSP-119. The CD28 -372G>A and CD40 -1C>T SNPs were associated with IgM prevalence against ICB2-5. Haplotypes formed by polymorphisms in CD28, CTLA4, and ICOS genes were associated with IgG4 antibodies against ICB2-5. This is the first study to associate polymorphisms in costimulatory genes with humoral immune response against P. vivax. These data may add important information for understanding the immunological aspects involved in vivax malaria