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
BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), infective dermatitis associated with HTLV-1 (IDH), and various other clinical conditions. Several of these diseases can occur in association. OBJECTIVE: Report an association of diseases related to HTLV-1 infection, occurring in an unusual age group. METHODS: Dermatological and laboratory exams were consecutively performed in HTLV-1-infected individuals from January 2008 to July 2010 in the HTLV Outpatient Clinic at the Institute of Infectious Diseases "Emilio Ribas" in São Paulo, Brazil. RESULTS: A total of 193 individuals (73 HAM/TSP and 120 asymptomatic carriers) were evaluated, three of which were associated with adult-onset IDH and HAM/TSP. In all three cases, the patients were affected by IDH after the development and progression of HAM/TSP-associated symptoms. LIMITATIONS: Small number of cases because of the rarity of these diseases. CONCLUSION: We draw attention to the possibility of co-presentation of adult-onset IDH in patients with a previous diagnosis of HAM/TSP, although IDH is a disease classically described in children. Thus, dermatologists should be aware of these diagnoses in areas endemic for HTLV-1 infection.