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CD80+ AND CD86+ B CELLS AS BIOMARKERS AND POSSIBLE THERAPEUTIC TARGETS IN HTLV-1 ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS AND MULTIPLE SCLEROSIS
HTLV-1
Multiple sclerosis
Interferon-alpha/beta
B cell
Costimulatory CD80
CD86
Human
Ex vivo
Disease severity
Gender
Autor
Afiliación
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil
INSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, France
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil
Bahiana School of Medicine and Public Health. Salvador-Bahia, Brazil
Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru
Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru
Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru / Departamento de Medicina. Facultad de Medicina Alberto Hurtado. Universidad Peruana Cayetano Heredia. Lima, Peru
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Instituto de Higiene e Medicina Tropical. Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia. Universidade Nova de Lisboa. Lisbon, Portugal
Bahiana School of Medicine and Public Health. Salvador, BA, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
INSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, France
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil / Institute for Immunological Investigation (iii-INCT). São Paulo, SP, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil
INSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, France
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil
Bahiana School of Medicine and Public Health. Salvador-Bahia, Brazil
Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru
Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru
Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Peru / Departamento de Medicina. Facultad de Medicina Alberto Hurtado. Universidad Peruana Cayetano Heredia. Lima, Peru
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Instituto de Higiene e Medicina Tropical. Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia. Universidade Nova de Lisboa. Lisbon, Portugal
Bahiana School of Medicine and Public Health. Salvador, BA, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
INSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, France
Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasil / Institute for Immunological Investigation (iii-INCT). São Paulo, SP, Brasil
Resumen en ingles
BACKGROUND: Human T-cell lymphotropic virus (HTLV-1) is the causative agent of the incapacitating, neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, there are no disease-modifying therapies with long-term clinical benefits or validated biomarkers for clinical follow-up in HAM/TSP. Although CD80 and CD86 costimulatory molecules play prominent roles in immune regulation and reflect disease status in multiple sclerosis (MS), data in HAM/TSP are lacking. METHODS: Using flow cytometry, we quantified ex vivo and in vitro expression of CD80 and CD86 in PBMCs of healthy controls, HTLV-1-infected individuals with and without HAM/TSP, and MS patients. We hypothesized ex vivo CD80 and CD86 expressions and their in vitro regulation by interferon (IFN)-α/ß mirror similarities between HAM/TSP and MS and hence might reveal clinically useful biomarkers in HAM/TSP. RESULTS: Ex vivo expression of CD80 and CD86 in T and B cells increased in all HTLV-1 infected individuals, but with a selective defect for B cell CD86 upregulation in HAM/TSP. Despite decreased total B cells with increasing disease duration (p = 0.0003, r = -0.72), CD80+ B cells positively correlated with disease severity (p = 0.0017, r = 0.69) in HAM/TSP. B cell CD80 expression was higher in women with HAM/TSP, underscoring that immune markers can reflect the female predominance observed in most autoimmune diseases. In contrast to MS patients, CD80+ (p = 0.0001) and CD86+ (p = 0.0054) lymphocytes expanded upon in vitro culture in HAM/TSP patients. The expansion of CD80+ and CD86+ T cells but not B cells was associated with increased proliferation in HTLV-1 infection. In vitro treatment with IFN-ß but not IFN-α resulted in a pronounced increase of B cell CD86 expression in healthy controls, as well as in patients with neuroinflammatory disease (HAM/TSP and MS), similar to in vivo treatment in MS. CONCLUSIONS: We propose two novel biomarkers, ex vivo CD80+ B cells positively correlating to disease severity and CD86+ B cells preferentially induced by IFN-ß, which restores defective upregulation in HAM/TSP. This study suggests a role for B cells in HAM/TSP pathogenesis and opens avenues to B cell targeting (with proven clinical benefit in MS) in HAM/TSP but also CD80-directed immunotherapy, unprecedented in both HAM/TSP and MS
Palabras clave en ingles
Neuroinflammatory diseaseHTLV-1
Multiple sclerosis
Interferon-alpha/beta
B cell
Costimulatory CD80
CD86
Human
Ex vivo
Disease severity
Gender
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