BackgroundThe antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials.Methods and FindingsIn this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3α and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1*01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein.ConclusionsHLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.

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References1 Fife KH, Ferenczy A, Douglas JM Jr, Brown DR, Smith M, Owens ML; HPV Study Group. Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day. Sex Transm Dis 2001; 28: 226-231. 2 Raasch B. Management of superficial basal cell carcinoma: focus on imiquimod. Clin Cosmet Investig Dermatol 2009; 11: 65-75. 3 Beutner KR, Spruance SL, Hougham AJ, Fox TL, Owens ML, Douglas JM Jr. Treatment of genital warts with an immune-response modifier (imiquimod).

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BackgroundHTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce.MethodsThe genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated.ResultsLack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers.ConclusionsWe did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.

BackgroundThe host immune response is an important indicator of the outcome of hepatitis C virus (HCV) infection and disease progression. The aim of this study was to explore cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV spontaneous clearance in a population from Rio de Janeiro, Brazil.MethodsGenetic polymorphisms in the cytokines, tumor necrosis factor-alpha (−308), transforming growth factor-beta 1 (codons 10 and 25), interleukin-10 (IL-10; −1082 and −592), IL-6 (−174), and interferon-gamma (+874) were analyzed by polymerase chain reaction sequence-specific primers in 245 patients with chronic hepatitis C (CHC), 41 spontaneous recovery (SR) patients, and 189 healthy volunteers. Further, polymorphisms in IL-28B (rs12979860, rs12980275, and rs8099917) were assessed by real-time polymerase chain reaction in all groups.ResultsThe IL-28B rs12979860 CC and rs12980275 AA genotypes were significantly associated with SR of HCV infection and response to therapy, whereas the C allele of IL-6 (−174) was associated with protection to CHC. A multivariate analysis showed that the male sex and IL-28B rs12979860 CT and TT and transforming growth factor-beta 1 (codon 10) TC genotypes were factors associated with CHC. Additionally, IL-6 (−174) C allele was increased in SR patients compared with patients with CHC.ConclusionIL-28B polymorphisms are associated with spontaneous clearance of HCV and response to therapy in a Brazilian population. Also, IL-6 (−174) C allele is involved in SR and decreased inflammation scores.

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