IL-10 predicts incident neuroinflammatory disease and proviral load dynamics in a large Brazilian cohort of people living with human T-lymphotropic virus type 1

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Assone, Tatiane ; Menezes, Soraya Maria ; Goncalves, Fernanda de Toledo ; Folgosi, Victor Angelo ; Braz, Marcos ; Smid, Jerusa ; Haziot, Michel E. ; Marcusso, Rosa M. N. ; Dahy, Flavia E. ; de Oliveira, Augusto Cesar Penalva ; Vanderlinden, Evelien ; Claes, Sandra ; Daelemans, Dirk ; Vercauteren, Jurgen ; Schols, Dominique ; Casseb, Jorge ; Van Weyenbergh, Johan

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 15, p. 9-pg., 2024-06-19.

Resumo

Human T-Lymphotropic Virus type-1 (HTLV-1) is a unique retrovirus associated with both leukemogenesis and a specific neuroinflammatory condition known as HTLV-1-Associated Myelopathy (HAM). Currently, most proposed HAM biomarkers require invasive CSF sampling, which is not suitable for large cohorts or repeated prospective screening. To identify non-invasive biomarkers for incident HAM in a large Brazilian cohort of PLwHTLV-1 (n=615 with 6,673 person-years of clinical follow-up), we selected all plasma samples available at the time of entry in the cohort (between 1997-2019), in which up to 43 cytokines/chemokines and immune mediators were measured. Thus, we selected 110 People Living with HTLV-1 (PLwHTLV-1), of which 68 were neurologically asymptomatic (AS) at baseline and 42 HAM patients. Nine incident HAM cases were identified among 68 AS during follow-up. Using multivariate logistic regression, we found that lower IL-10, IL-4 and female sex were independent predictors of clinical progression to definite HAM (AUROC 0.91), and outperformed previously suggested biomarkers age, sex and proviral load (AUROC 0.77). Moreover, baseline IL-10 significantly predicted proviral load dynamics at follow-up in all PLwHTLV-1. In an exploratory analysis, we identified additional plasma biomarkers which were able to discriminate iHAM from either AS (IL6R alpha, IL-27) or HAM (IL-29/IFN-lambda 1, Osteopontin, and TNFR2). In conclusion, female sex and low anti-inflammatory IL-10 and IL-4 are independent risk factors for incident HAM in PLwHTLV-1,while proviral load is not, in agreement with IL-10 being upstream of proviral load dynamics. Additional candidate biomarkers IL-29/IL-6R/TNFR2 represent plausible therapeutic targets for future clinical trials in HAM patients. (AU)

• Processo FAPESP: 16/03025-2 - Identificação de polimorfismos relacionados à mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP)
• Beneficiário: Tatiane Assone Casseb
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/18522-0 - Análise genômica, transcriptômica e metabolômica integrada de mecanismos (imuno) patogênicos que conduzem à paraparesia espástica tropical / mielopatia associada ao HTLV-1 (HAM/TSP)
• Beneficiário: Tatiane Assone Casseb
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado