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LACK OF ASSOCIATION BETWEEN SINGLE-NUCLEOTIDE POLYMORPHISMS OF PRO- AND ANTI-INFLAMMATORY CYTOKINES AND HTLV-1-ASSOCIATED MYELOPATHY / TROPICAL SPASTIC PARAPARESIS DEVELOPMENT IN PATIENTS FROM RIO DE JANEIRO, BRAZIL
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Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Rio de Janeiro State University. Policlinica Piquet Carneiro. Histocompatibility and Cryopreservation Laboratory. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Plataforma de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil
Rio de Janeiro State University. Policlinica Piquet Carneiro. Histocompatibility and Cryopreservation Laboratory. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Rio de Janeiro State University. Policlinica Piquet Carneiro. Histocompatibility and Cryopreservation Laboratory. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Plataforma de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil
Rio de Janeiro State University. Policlinica Piquet Carneiro. Histocompatibility and Cryopreservation Laboratory. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Abstract
Background: HTLV-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. Methods: The 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. Results: Lack 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. Conclusions: We 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.
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