Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects

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Assone, Tatiane ; Malta, Fernanda M. ; Bakkour, Sonia ; Montalvo, Leilani ; Paiva, Arthur M. ; Smid, Jerusa ; Penalva de Oliveira, Augusto Cesar ; Goncalves, Fernanda de Toledo ; Luiz, Olinda do Carmo ; Fonseca, Luiz Augusto M. ; Norris, Philip J. ; Casseb, Jorge

• Tipo de documento: Artigo Científico
• Fonte: VIRUS RESEARCH; v. 244, p. 4-pg., 2018-01-15.

Resumo

Introduction: Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. Methods: 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases "Emilio Ribas" (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-lambda 4, HLA-C and KIR genotypes using qPCR. Results: We found associations between LPA (p = 0.0001) with HAM/TSP and confirmed the IFN-lambda 4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR = 3.22, CI = 1.10-9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. Conclusion: We demonstrated that age, LPA and an IFN-lambda 4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future. (AU)

• Processo FAPESP: 12/23397-0 - Determinação do perfil do polimorfismo da IL28B em indivíduos co-infectados pelo Vírus da Hepatite C crônica (HCV) e pelo vírus linfotrópico de células T humanas tipo 1 (HTLV-1)
• Beneficiário: Jorge Simao do Rosario Casseb
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/22827-7 - Prevalência e incidência de alteração precoce no sistema nervoso central em pessoas infectados pelo HTLV-1
• Beneficiário: Jorge Simao do Rosario Casseb
• Modalidade de apoio: Auxílio à Pesquisa - Regular