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-λ4, HLA-C and KIR genotypes using qPCR. RESULTS: We found associations between LPA (p=0.0001) with HAM/TSP and confirmed the IFN-λ4 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-λ4 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.
Assuntos
Antígenos HLA-C/genética , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Interleucinas/genética , Paraparesia Espástica Tropical/genética , Receptores KIR/genética , Adulto , Idoso , Doenças Assintomáticas , Proliferação de Células , Progressão da Doença , Feminino , Expressão Gênica , Antígenos HLA-C/imunologia , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/patologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Interleucinas/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/patologia , Polimorfismo Genético , Prognóstico , Receptores KIR/imunologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Carga ViralRESUMO
Human T-lymphotropic virus type 1 (HTLV-1) is a type C retrovirus primarily endemic to Japan, Central and South America, the Middle East, regions of Africa, and the Caribbean. Currently, an estimated 10-20 million people worldwide are infected with this virus. Although the majority of infected individuals remain asymptomatic, HTLV-1 is the causative agent of a number of disorders, notably adult T-cell leukemia/lymphoma (ATLL) and a progressive demyelinating neurological disorder, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition to ATLL and HAM/TSP, HTLV-1 has been associated with a spectrum of skin disorders, such as infective dermatitis associated with HTLV-1, crusted scabies, and leprosy. The understanding of the interaction between virus and host response has improved markedly, but there are still few treatment options.