CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
| Autor: | Ramon de Almeida Kruschewsky, Saul Velloso Schnitman, Carolina Alvarez, Daniele Decanine, Johan Van Weyenbergh, David Brassat, Giovanni López, Roland S. Liblau, Anne-Mieke Vandamme, Soraya Maria Menezes, Michael Talledo, Ricardo Khouri, Bernardo Galvão-Castro, Eduardo Gotuzzo |
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| Přispěvatelé: | Department of Microbiology and Immunology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Microbiology and Immunoregulation of Integrate Laboratory [Salvador, Brésil] (LIMI), Instituto Gonçalo Moniz / Gonçalo Moniz Research Centre - Fiocruz Bahia [Salvador, Brésil] (IGM), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH), Departamento de Medicina, Facultad de Medicina Alberto Hurtado-Universidad Peruana Cayetano Heredia (UPCH), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratório Avançado de Saúde Pública / Advanced Laboratory of Public Health [Salvador, Brésil] (LASP), Institute for Investigation in Immunology (iii-INCT), National Institutes of Science and Technology (INCT), This research was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), Brazil, Fonds voor Wetenschappelijk Onderzoek - Flanders (FWO) grant G.0778.10N, VLIR-UOS project ZEIN2010PR376 and the 'Leerstoel voor Wetenschappelijk onderzoek over infectieziekten in ontwikkelingslanden' from KU Leuven, Belgium, BMC, Ed. |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
peripheral blood mononuclear cell purl.org/pe-repo/ocde/ford#3.02.25 [https] medicine.medical_treatment [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ex vivo study B7 antigen Interferon-alpha/beta multiple sclerosis Severity of Illness Index Interferon immune system diseases Tropical spastic paraparesis Antigens CD80 T lymphocyte CD86 Cells Cultured clinical article tropical spastic paraparesis B cell B-Lymphocytes General Neuroscience adult article virus diseases hemic and immune systems Middle Aged biological marker Flow Cytometry Antigens CD86 Paraparesis Tropical Spastic alpha interferon 3. Good health purl.org/pe-repo/ocde/ford#3.01.03 [https] medicine.anatomical_structure female Neurology beta interferon B7-1 Antigen [SDV.IMM]Life Sciences [q-bio]/Immunology Female disease severity Biological Markers immunotherapy cell expansion medicine.drug Human Adult endocrine system in vitro study [SDV.IMM] Life Sciences [q-bio]/Immunology immunoregulation sex difference Immunology chemical and pharmacologic phenomena autoimmune disease lymphocyte proliferation CD86 antigen Multiple sclerosis Cellular and Molecular Neuroscience Sex Factors medicine Humans Neuroinflammatory disease Disease severity B lymphocyte business.industry Research human cell [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Gender drug targeting Immunotherapy purl.org/pe-repo/ocde/ford#3.01.04 [https] Costimulatory CD80 medicine.disease HTLV-I Infections Ex vivo HTLV-1 Leukocytes Mononuclear antigen expression B7-2 Antigen disease duration business CD80 Biomarkers upregulation |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, 2014, 11 (1), pp.18. ⟨10.1186/1742-2094-11-18⟩ Journal of Neuroinflammation, BioMed Central, 2014, 11 (1), pp.18. ⟨10.1186/1742-2094-11-18⟩ |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/1742-2094-11-18⟩ |
| Popis: | 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/β 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-β 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-β, 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. |
| Databáze: | OpenAIRE |
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