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An integrated genomic, transcriptomic and metabolomic analysis of (immuno)pathogenic mechanisms leading to HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Grant number: 19/18522-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): December 16, 2019
Effective date (End): December 15, 2020
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Jorge Simão do Rosário Casseb
Grantee:Tatiane Assone dos Santos
Supervisor abroad: Johan Van Weyenbergh
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Leuven (KU Leuven), Belgium  
Associated to the scholarship:16/03025-2 - Identification of polymorphisms related to HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM / TSP), BP.PD

Abstract

Introduction: HTLV-1 was described in 1980 and identified as the causative agent of ATL and HAM/TSP, in addition to other inflammatory diseases. It is estimated that 15 to 25 million people worldwide are infected with HTLV-1. However, most of them remain asymptomatic. Host immune and genetic factors have been associated to HAM/TSP pathogenesis, but large genome-wide studiesare lacking. Objective: To analyze whether there is an association between genome-wide genetic variation and HAM/TSP susceptibility in individuals infected with HTLV-1. Material and Methods: Volunteers were recruited from the HTLV outpatient clinic of the "Emílio Ribas" Institute of Infectious Diseases (IIER). A total of 1000 volunteers have been recruited for this study 600 asymptomatics (controls) and 400 HAM/TSP patients (cases). Genome-Wide Association Analysis (GWAS) has been performed on all 1000 cases and will be combined with data from bioassays (HTLV-1 proviral load and spontaneous T cell proliferation), transcriptomics and metabolomics in a subset of patients.. Besides descriptive, univariate and multivariate statistics, systems biology analysis and data mining will combine cross-omics data . Conclusion: These data will provide the first GWAS and cross-omics analysis of HAM/TSP, providing insight into its immunopathogenesis, and possibly revealing novel immunotherapeutic strategiesfor its clinical management.