|
Título:
|
CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis
|
|
Autores:
|
Menezes, S.M. ;
Decanine, D. ;
Brassat, D. ;
Khouri, R. ;
Schnitman, S.V. ;
Kruschewsky, R. ;
López, G. ;
Álvarez, C. ;
Talledo, M. ;
Gotuzzo, E. ;
Vandamme, A.-M. ;
Galvão-Castro, B. ;
Liblau, R. ;
Weyenbergh, J.V.
|
|
Tipo de documento:
|
texto impreso
|
|
Editorial:
|
BMC, 2020-06-10T18:12:16Z
|
|
Nota general:
|
info:eu-repo/semantics/restrictedAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
|
|
Idiomas:
|
Inglés
|
|
Palabras clave:
|
Editados por otras instituciones
,
Artículos
,
Artículos en revistas indizadas
|
|
Resumen:
|
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)-?/? 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-? but not IFN-? 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-?, 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. © 2014 Menezes et al.; licensee BioMed Central Ltd.
|
|
En línea:
|
http://doi.org/10.1186/1742-2094-11-18
|
