Polimorfismos do gene CTLA4 associado na regulação de células T na resposta imune em indivíduos naturalmente infectados pelo Plasmodium vivax no Estado do Pará

Abstract

Plasmodium vivax is the most common cause of human malarial parasite infection in the Brazilian Amazon region. Cell-mediated immunity requires costimulatory activity to initiate or inhibit antigen-specific T-cell responses. Cytotoxic T lymphocyte-associated antigen (CTLA)-4 is an inhibitory receptor expressed by activated and regulatory T cells. The aim of this study was to analyze two coding single-nucleotide polymorphisms (SNPs) in CTLA4 in patients with P. vivax malaria and their correlation with parasitaemia and plasma interleukin (IL)-4 levels. Methods: A total of 182 P. vivax malaria patients were enrolled in the study. DNA was extracted from blood samples using a standard procedure. A PCR-RFLP protocol was used to identify the genotype and allele frequencies of the polymorphisms. The density of parasitemia in the infected individuals was recorded and expressed as the number of asexual P. vivax per microliter of blood assuming a count of 100 microscopy fields and estimated before treatment. Serum levels of IL-4 were detected using a Milliplex Map kit (Human Cytokine/Chemokine Magnetic Bead Panel–HCYTOMAG-60K) and a Magpix/Luminex®. Analyses were performed using R version 2.8.1 statistical software. Results: For the polymorphism at position -1577 G/A, the G/A genotype had the highest frequency (49.4%), followed by the G/G genotype (41%) and the A/A genotype (9.6%). For the polymorphism at position -1722 T/C, the T/T genotype had the highest frequency (86.7%), followed by the T/C genotype (12.3%), and the least frequent was the C/C genotype (1%). The IL-4 plasma level ranged from 0.61 to 9.32 pg/mL. There were no statistically significant differences in either parasitaemia or plasma IL-4 levels among individuals with different genotypes. Conclusion: The study also highlights the importance of conducting genetic association studies in different ethnic populations. CTLA4 SNPs may be associated with malaria vivax in other endemic areas and other parasitic diseases, but they appear to have no such effect in this studied population.