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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

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dc.contributor.author Menezes, Soraya Maria
dc.contributor.author Decanine, Daniele
dc.contributor.author Brassat, David
dc.contributor.author Khouri, Ricardo
dc.contributor.author Schnitman, Saul V.
dc.contributor.author Kruschewsky, Ramon
dc.contributor.author López, Giovanni
dc.contributor.author Alvarez, Carolina
dc.contributor.author Talledo Albujar, Michael John
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author Vandamme, Anne-Mieke
dc.contributor.author Galvão-Castro, Bernardo
dc.contributor.author Liblau, Roland
dc.contributor.author Weyenbergh, Johan Van
dc.date.accessioned 2020-06-10T18:12:16Z
dc.date.available 2020-06-10T18:12:16Z
dc.date.issued 2014
dc.identifier.uri https://hdl.handle.net/20.500.12866/8080
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartofseries Journal of Neuroinflammation
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Adult en_US
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Middle Aged en_US
dc.subject Gender en_US
dc.subject Severity of Illness Index en_US
dc.subject Sex Factors en_US
dc.subject HTLV-I Infections en_US
dc.subject human en_US
dc.subject adult en_US
dc.subject female en_US
dc.subject male en_US
dc.subject Multiple sclerosis en_US
dc.subject multiple sclerosis en_US
dc.subject article en_US
dc.subject sex difference en_US
dc.subject biological marker en_US
dc.subject disease severity en_US
dc.subject Cells, Cultured en_US
dc.subject Leukocytes, Mononuclear en_US
dc.subject Flow Cytometry en_US
dc.subject HTLV-1 en_US
dc.subject clinical article en_US
dc.subject disease duration en_US
dc.subject T lymphocyte en_US
dc.subject autoimmune disease en_US
dc.subject in vitro study en_US
dc.subject human cell en_US
dc.subject tropical spastic paraparesis en_US
dc.subject flow cytometry en_US
dc.subject B lymphocyte en_US
dc.subject upregulation en_US
dc.subject antigen expression en_US
dc.subject peripheral blood mononuclear cell en_US
dc.subject drug targeting en_US
dc.subject CD86 antigen en_US
dc.subject Paraparesis, Tropical Spastic en_US
dc.subject Multiple Sclerosis en_US
dc.subject Biological Markers en_US
dc.subject ex vivo study en_US
dc.subject beta interferon en_US
dc.subject alpha interferon en_US
dc.subject Antigens, CD80 en_US
dc.subject Antigens, CD86 en_US
dc.subject B cell en_US
dc.subject B-Lymphocytes en_US
dc.subject B7 antigen en_US
dc.subject CD86 en_US
dc.subject cell expansion en_US
dc.subject Costimulatory CD80 en_US
dc.subject Disease severity en_US
dc.subject Ex vivo en_US
dc.subject Human en_US
dc.subject immunoregulation en_US
dc.subject immunotherapy en_US
dc.subject Interferon-alpha/beta en_US
dc.subject lymphocyte proliferation en_US
dc.subject Neuroinflammatory disease en_US
dc.title CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1186/1742-2094-11-18
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.25
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.04
dc.relation.issn 1742-2094

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