Tatiane Assone1, Fernanda M Malta2, Sonia Bakkour3, Leilani Montalvo3, Arthur M Paiva1, Jerusa Smid4, Augusto César Penalva de Oliveira4, Fernanda de Toledo Gonçalves5, Olinda do Carmo Luiz6, Luiz Augusto M Fonseca6, Philip J Norris7, Jorge Casseb8. 1. Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, University of São Paulo Medical School, Brazil; Institute of Tropical Medicine of São Paulo, University of São Paulo, Brazil. 2. Institute of Tropical Medicine of São Paulo, University of São Paulo, Brazil; Department of Gastroenterology, Laboratory of Gastroenterology and Tropical Hepatology, University of São Paulo Medical School, Brazil. 3. Blood Systems Research Institute, San Francisco, CA, USA. 4. Institute Infectious of Diseases "Emilio Ribas" (IIER), São Paulo, Brazil. 5. Laboratory of Immunohematology and Forensic Hematology-LIM40, Department of Forensic Medicine, Medical Ethics, Social Medicine and Work, University of São Paulo Medical School, Brazil. 6. Department of Preventive Medicine, University of São Paulo Medical School (LIM 38), Brazil. 7. Blood Systems Research Institute, San Francisco, CA, USA; University of California, San Francisco, CA, USA. 8. Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, University of São Paulo Medical School, Brazil; Institute of Tropical Medicine of São Paulo, University of São Paulo, Brazil. Electronic address: jcasseb10@gmail.com.
Abstract
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.
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/TSPpatients). 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.
Authors: Maria Alice Freitas Queiroz; Ednelza da Silva Graça Amoras; Tuane Carolina Ferreira Moura; Carlos Araújo da Costa; Maisa Silva de Sousa; Sandra Souza Lima; Ricardo Ishak; Antonio Carlos Rosário Vallinoto Journal: Front Cell Infect Microbiol Date: 2020-05-25 Impact factor: 5.293
Authors: Denis de Castro Silva; Ednelza da Silva Graça Amoras; Tuane Carolina Ferreira Moura; Felipe Teixeira Lopes; Samara Tatielle Monteiro Gomes; Carlos A da Costa; Maísa Silva Sousa; Ricardo Ishak; Antonio Carlos Rosário Vallinoto; Maria Alice Freitas Queiroz Journal: Viruses Date: 2019-12-19 Impact factor: 5.048
Authors: Antonio Carlos Rosário Vallinoto; Izaura Cayres-Vallinoto; Maria Alice Freitas Queiroz; Marluísa de Oliveira Guimarães Ishak; Ricardo Ishak Journal: Viruses Date: 2019-10-23 Impact factor: 5.048
Authors: Rosa Maria N Marcusso; Johan Van Weyenbergh; João Victor Luisi de Moura; Flávia Esper Dahy; Aline de Moura Brasil Matos; Michel E J Haziot; Jose E Vidal; Luiz Augusto M Fonseca; Jerusa Smid; Tatiane Assone; Jorge Casseb; Augusto César Penalva de Oliveira Journal: Pathogens Date: 2019-12-26