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AutorMenezes, Soraya Maria
AutorDecanine, Daniele
AutorBrassat, David
AutorCunha, Antonio Ricardo Khouri
AutorSchnitman, Saul V.
AutorKruschewsky, Ramon de Almeida
AutorLópez, Giovanni
AutorAlvarez, Carolina
AutorTalledo, Michael
AutorGotuzzo, Eduardo
AutorVandamme, Anne-Mieke
AutorCastro Filho, Bernardo Galvão
AutorLiblau, Roland
AutorWeyenbergh, Johan Van
Fecha de acceso2014-05-09T13:13:34Z
Fecha de disponibilización2014-05-09T13:13:34Z
Fecha de publicación2014
ReferenciaMENEZES, S. M. et al. CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy tropical spastic paraparesis and multiple sclerosis. Journal of Neuroinflammation, v.11, n.18, p. 18, 2014.pt_BR
ISSN1742-2094
URIhttps://www.arca.fiocruz.br/handle/icict/7595
Idiomaengpt_BR
EditorBioMed Centralpt_BR
Derechos de autoropen accesspt_BR
TítuloCD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosispt_BR
Tipo del documentoArticlept_BR
Resumen en InglésBACKGROUND: 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 MSpt_BR
AfiliaciónDepartment of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgiumpt_BR
AfiliaciónFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasilpt_BR
AfiliaciónINSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, Francept_BR
AfiliaciónDepartment 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, Brasilpt_BR
AfiliaciónFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, Brasilpt_BR
AfiliaciónBahiana School of Medicine and Public Health. Salvador-Bahia, Brazilpt_BR
AfiliaciónInstituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Perupt_BR
AfiliaciónDepartment 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, Perupt_BR
AfiliaciónInstituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, Perupt_BR
AfiliaciónInstituto 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, Perupt_BR
AfiliaciónDepartment 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, Portugalpt_BR
AfiliaciónBahiana School of Medicine and Public Health. Salvador, BA, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasilpt_BR
AfiliaciónINSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, Francept_BR
AfiliaciónDepartment 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, Brasilpt_BR
Palavras clave en InglêsNeuroinflammatory diseasept_BR
Palavras clave en InglêsHTLV-1pt_BR
Palavras clave en InglêsMultiple sclerosispt_BR
Palavras clave en InglêsInterferon-alpha/betapt_BR
Palavras clave en InglêsB cellpt_BR
Palavras clave en InglêsCostimulatory CD80pt_BR
Palavras clave en InglêsCD86pt_BR
Palavras clave en InglêsHumanpt_BR
Palavras clave en InglêsEx vivopt_BR
Palavras clave en InglêsDisease severitypt_BR
Palavras clave en InglêsGenderpt_BR
xmlui.metadata.dc.subject.ods05 Igualdade de gênero


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