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

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.
Type de document :
Article dans une revue
Journal of Neuroinflammation, BioMed Central, 2014, 11 (1), pp.18. 〈10.1186/1742-2094-11-18〉
Liste complète des métadonnées

Littérature citée [130 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00945686
Contributeur : Ed. Bmc <>
Soumis le : mercredi 12 février 2014 - 16:53:54
Dernière modification le : jeudi 11 janvier 2018 - 06:23:24
Document(s) archivé(s) le : mardi 13 mai 2014 - 11:27:02

Fichiers

Identifiants

Collections

Citation

Soraya Menezes, Daniele Decanine, David Brassat, Ricardo Khouri, Saul Schnitman, 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, BioMed Central, 2014, 11 (1), pp.18. 〈10.1186/1742-2094-11-18〉. 〈inserm-00945686〉

Partager

Métriques

Consultations de la notice

402

Téléchargements de fichiers

195