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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 Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): December 16, 2019
Effective date (End): December 11, 2020
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Jorge Simão do Rosário Casseb
Grantee:Tatiane Assone Casseb
Supervisor: Johan Van Weyenbergh
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Leuven, 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


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.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA SILVA PRATES, GABRIELA; MALTA, FERNANDA M.; DE TOLEDO GONCALVES, FERNANDA; MONTEIRO, MARIANA A.; FONSECA, LUIZ AUGUSTO M.; R. VEIGA, ANA PAULA; M. C. MAGRI, MARCELLO; DUARTE, ALBERTO J. S.; CASSEB, JORGE; ASSONE, TATIANE; et al. AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from Sao Paulo, Brazil: The role of IFN-lambda 4 polymorphisms. Journal of Medical Virology, v. 93, n. 6, p. 3601-3606, . (16/03025-2, 19/18522-0, 17/08320-5, 18/07239-2)

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