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Conselho Nacional para o Desenvolvimento Cient?fico e Tecnol?gico (CNPq) ; Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior, Brazil (CAPES ? DS and PDSE) ? Finance Code 001 S?o Paulo State University. Graduate Program in Biosciences. S?o Jos? do Rio Preto, SP, Brazil. Lisboa University. Tropical Medicine and Hygiene Institut. Global Health and Tropical Medicine. Lisboa, Portugal. Federal University of Sergipe. Department of Biology. Aracaj?, SE, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Imunogen?tica da Mal?ria Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Microscopia Eletr?nica. Ananindeua, PA, Brasil / Universidade Federal do Par?. Bel?m, PA, Brasil. Fluminense Federal University. Center of Microorganisms Investigation. Niter?i, RJ, Brazil. Fluminense Federal University. Center of Microorganisms Investigation. Niter?i, RJ, Brazil. Fluminense Federal University. Center of Microorganisms Investigation. Niter?i, RJ, Brazil. Funda??o Oswaldo Cruz. Oswaldo Cruz Institute. Laboratory of Malaria Research. Rio de Janeiro, RJ, Brazil. S?o Paulo State University. Graduate Program in Biosciences. S?o Jos? do Rio Preto, SP, Brazil. Funda??o Oswaldo Cruz. Oswaldo Cruz Institute. Laboratory of Immunoparasitology. Rio de Janeiro, RJ, Brazil. S?o Paulo State University. Graduate Program in Biosciences. S?o Jos? do Rio Preto, SP, Brazil / Fluminense Federal University. Center of Microorganisms Investigation. Niter?i, RJ, Brazil. BACKGROUND: It is well established that infection by Plasmodium vivax is a result of host-parasite interactions. In the present study, association with the IL1/IL2 cytokine profiles, anticircumsporozoite protein antibody levels and parasitic loads was evaluated in individuals naturally infected with P. vivax in an endemic area of the Brazilian Amazon. METHODS: Molecular diagnosis of P. vivax and variants was performed using the PCR-RFLP method and IL1B -511C>T, IL2 -330T>G and IL2+114T>G polymorphisms were identified using PCR-RFLP and allele-specific PCR. IL-1? and IL-2 cytokine levels were detected by flow cytometry and circumsporozoite protein (CSP) antibodies were measured by ELISA. RESULTS: Three variants of P. vivax CSP were identified and VK247 was found to be the most frequent. However, the prevalence and magnitude of IgG antibodies were higher for the VK210 variant. Furthermore, the antibody response to the CSP variants was not associated with the presence of the variant in the infection. Significant differences were observed between the single nucleotide polymorphism (SNP) -511T>C in the IL1B gene and levels of antibodies to the VK247 and P. vivax-like variants, but there were no associations between SNPs in IL1 and IL2 genes and their plasma products. CONCLUSIONS: Individuals with the rs16944 CC genotype in the IL1? gene have higher antibody levels to the CSP of P. vivax of VK247 and P. vivax-like variants.

Made available in DSpace on 2018-11-26T15:28:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-11-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Co-stimulatory molecules are essential in the orchestration of immune response and polymorphisms in their genes are associated with various diseases. However, in the case of variable allele frequencies among continental populations, this variation can lead to biases in genetic studies conducted in admixed populations such as those from Brazil. The aim of this study was to evaluate the influence of genomic ancestry on distributions of co-stimulatory genes polymorphisms in an admixed Brazilian population. A total of 273 individuals from the north of Brazil participated in this study. Nine single nucleotide polymorphisms in 7 genes (CD28, CTLA4, ICOS, CD86, CD40, CD40L and BLYS) were determined by polymerase chain reaction-restriction fragment length polymorphism. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. The analysis showed that the main contribution was European (43.9%) but also a significant contribution of African (31.6%) and Amerindian (24.5%) ancestry. ICOS, CD40L and CD86 polymorphisms were associated with genomic ancestry. However there were no significant differences in the proportions of ancestry for the other SNPs and haplotypes studied. Our findings reinforce the need to apply AIMs in genetic association studies involving these polymorphisms in the Brazilian population. (c) 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, Sao Jose Do Rio Preto, Brazil Fac Med Sao Jose do Rio Preto, Ctr Invest Microrganismos, Sao Jose Do Rio Preto, Brazil Fed Univ Para, Inst Ciencias Biol, BR-66059 Belem, Para, Brazil Univ Fed Sergipe, Dept Biol, Aracaju, Brazil Fed Univ Para, Lab Genet Humana & Med, BR-66059 Belem, Para, Brazil Secretaria Vigilancia Saude, Inst Evandro Chagas, Lab Pesquisas Basicas Malaria, Ananindeua, Brazil Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, Sao Jose Do Rio Preto, Brazil CNPq: 471605/2011-5

Background Plasmodium vivax is the most prevalent malaria species in Brazil. The parasite-host coevolutionary process can be viewed as an 'arms race', in which adaptive genetic changes in one are eventually matched by alterations in the other. Methods Following the candidate gene approach we analyzed the CD40, CD40L and BLYS genes that participate in B-cell co-stimulation, for associations with P. vivax malaria. The study sample included 97 patients and 103 controls. We extracted DNA using the extraction and purification commercial kit and identified the following SNPs: -1C > T in the CD40 gene, -726T > C in the CD40L gene and the -871C > T in the BLyS gene using PCR-RFLP. We analyzed the genotype and allele frequencies by direct counting. We also compared the observed with the expected genotype frequencies using the Hardy-Weinberg equilibrium. Results The allele and genotype frequencies for these SNPs did not differ statistically between patient and control groups. Gene-gene interactions were not observed between the CD40 and BLYS and between the CD40L and BLYS genes. Overall, the genes were in Hardy-Weinberg equilibrium. Significant differences were not observed among the frequencies of antibody responses against P. vivax sporozoite and erythrocytic antigens and the CD40 and BLYS genotypes. Conclusions The results of this study show that, although the investigated CD40, CD40L and BLYS alleles differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere in susceptibility to the disease. The variants of these genes may influence the clinical course rather than simply increase or decrease susceptibility.

Interleukin 2 (IL-2) is a monomeric glycoprotein that is primarily produced by activated CD4+ T cells, CD8+ T cells and dendritic cells. It is characterized as a proinflammatory cytokine that is secreted by Th1 cells. IL-2 plays a central role in the activation of regulatory T cells to produce the cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). IL-2 may also enhance the cytolytic activity of natural killer cells, thereby ensuring their significance in the control of the immune response, and effectively participate in the pathogenesis of several pathological conditions, such as cancer and metabolic, infectious, autoimmune and inflammatory diseases. We emphasize the importance of studies of IL-2 and discuss perspectives resulting from our increasing understanding of genetic diversity and its role in the immune response.

Background Several studies have recently demonstrated that the immune responses against malaria is governed by different factors, including the genetic components of the host. The IL-4 gene appears to be a strong candidate factor because of its role in the regulation of the Th2 response. The present study investigated the role of IL-4 polymorphisms in the development of IgG antibodies against PvAMA-1 and the IL-4 levels in individuals infected with Plasmodium vivax in a malaria endemic area in the Brazilian Amazon. Methods The study sample included 83 patients who were diagnosed with P. vivax infection using thick smear and confirmed by nested-PCR. The IL-4 −590 C>T and IL-4 −33 C>T polymorphisms were genotyped by PCR–RFLP, and the intron 3 VNTR was genotyped by PCR. A standardised ELISA protocol was used to measure the total IgG against PvAMA-1. The cytokine/chemokine levels were measured using a Milliplex multiplex assay (Millipore). All of the subjects were genotyped with 48 ancestry informative markers to determine the proportions of African, European and Amerindian ancestry using STRUCTURE software. Results Of the 83 patients, 60 (73%) produced IgG antibodies against PvAMA-1. A significant decrease in the percentage of respondents was observed among the primo-infected individuals. No significant differences were observed in the frequencies of genotypes and haplotypes among individuals who were positive or negative for IgG antibodies against PvAMA-1. Furthermore, no significant correlation was observed between the IL-4 polymorphisms, antibody levels, IL-4 levels, and parasitemia. Conclusions This study indicated that the polymorphisms identified in the IL-4 gene are not likely to play a role in the regulation of the antibody response against PvAMA-1 and IL-4 production in vivax malaria.