CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis

Detalhes bibliográficos
Autor(a) principal: Menezes, Soraya Maria
Data de Publicação: 2014
Outros Autores: Decanine, Daniele, Brassat, David, Cunha, Antonio Ricardo Khouri, Schnitman, Saul V., Kruschewsky, Ramon de Almeida, López, Giovanni, Alvarez, Carolina, Talledo, Michael, Gotuzzo, Eduardo, Vandamme, Anne-Mieke, Castro Filho, Bernardo Galvão, Liblau, Roland, Weyenbergh, Johan Van
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/7595
Resumo: Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium
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spelling Menezes, Soraya MariaDecanine, DanieleBrassat, DavidCunha, Antonio Ricardo KhouriSchnitman, Saul V.Kruschewsky, Ramon de AlmeidaLópez, GiovanniAlvarez, CarolinaTalledo, MichaelGotuzzo, EduardoVandamme, Anne-MiekeCastro Filho, Bernardo GalvãoLiblau, RolandWeyenbergh, Johan Van2014-05-09T13:13:34Z2014-05-09T13:13:34Z2014MENEZES, 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, 2014.1742-2094https://www.arca.fiocruz.br/handle/icict/7595engBioMed CentralCD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, BelgiumFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, BrasilINSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, FranceDepartment 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, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Integrado de Microbiologia e Imunoregulação. Salvador, BA, BrasilBahiana School of Medicine and Public Health. Salvador-Bahia, BrazilInstituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, PeruDepartment 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, PeruInstituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia. Lima, PeruInstituto 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, PeruDepartment 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, PortugalBahiana School of Medicine and Public Health. Salvador, BA, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, BrasilINSERM UMR and Pôle des Neurosciences. Hôpital Purpan. Université de Toulouse. Toulouse, FranceDepartment 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, BrasilBACKGROUND: 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 MSNeuroinflammatory diseaseHTLV-1Multiple sclerosisInterferon-alpha/betaB cellCostimulatory CD80CD86HumanEx vivoDisease severityGenderinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALMenezes SM CD80+ and CD86+....pdfMenezes SM CD80+ and CD86+....pdfapplication/pdf1147929https://www.arca.fiocruz.br/bitstream/icict/7595/1/Menezes%20SM%20CD80%2b%20and%20CD86%2b....pdf9de312fc3a753bfa46f2fd2f8e2b44f5MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/7595/2/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD52TEXTMenezes SM CD80+ and CD86+....pdf.txtMenezes SM CD80+ and CD86+....pdf.txtExtracted texttext/plain80352https://www.arca.fiocruz.br/bitstream/icict/7595/5/Menezes%20SM%20CD80%2b%20and%20CD86%2b....pdf.txt152bf61de43ffe73b57b30c2b3e08288MD55THUMBNAILMenezes SM CD80+ and CD86+....pdf.jpgMenezes SM CD80+ and CD86+....pdf.jpgGenerated Thumbnailimage/jpeg2174https://www.arca.fiocruz.br/bitstream/icict/7595/4/Menezes%20SM%20CD80%2b%20and%20CD86%2b....pdf.jpgc40e900856f1eddb55bd5d70f8b6c963MD54icict/75952023-03-15 14:33:11.471oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:11Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
title CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
spellingShingle CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
Menezes, Soraya Maria
Neuroinflammatory disease
HTLV-1
Multiple sclerosis
Interferon-alpha/beta
B cell
Costimulatory CD80
CD86
Human
Ex vivo
Disease severity
Gender
title_short CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
title_full CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
title_fullStr CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
title_full_unstemmed CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
title_sort CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
author Menezes, Soraya Maria
author_facet Menezes, Soraya Maria
Decanine, Daniele
Brassat, David
Cunha, Antonio Ricardo Khouri
Schnitman, Saul V.
Kruschewsky, Ramon de Almeida
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Vandamme, Anne-Mieke
Castro Filho, Bernardo Galvão
Liblau, Roland
Weyenbergh, Johan Van
author_role author
author2 Decanine, Daniele
Brassat, David
Cunha, Antonio Ricardo Khouri
Schnitman, Saul V.
Kruschewsky, Ramon de Almeida
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Vandamme, Anne-Mieke
Castro Filho, Bernardo Galvão
Liblau, Roland
Weyenbergh, Johan Van
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Menezes, Soraya Maria
Decanine, Daniele
Brassat, David
Cunha, Antonio Ricardo Khouri
Schnitman, Saul V.
Kruschewsky, Ramon de Almeida
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Vandamme, Anne-Mieke
Castro Filho, Bernardo Galvão
Liblau, Roland
Weyenbergh, Johan Van
dc.subject.en.pt_BR.fl_str_mv Neuroinflammatory disease
HTLV-1
Multiple sclerosis
Interferon-alpha/beta
B cell
Costimulatory CD80
CD86
Human
Ex vivo
Disease severity
Gender
topic Neuroinflammatory disease
HTLV-1
Multiple sclerosis
Interferon-alpha/beta
B cell
Costimulatory CD80
CD86
Human
Ex vivo
Disease severity
Gender
description Department of Microbiology and Immunology. Rega Institute for Medical Research. KU Leuven, Leuven, Belgium
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-05-09T13:13:34Z
dc.date.available.fl_str_mv 2014-05-09T13:13:34Z
dc.date.issued.fl_str_mv 2014
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MENEZES, 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/7595
dc.identifier.issn.none.fl_str_mv 1742-2094
identifier_str_mv MENEZES, 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.
1742-2094
url https://www.arca.fiocruz.br/handle/icict/7595
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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