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

Johan Van Weyenbergh⁶  Roland Liblau⁴  Bernardo Galvão-Castro²  Anne-Mieke Vandamme⁷  Eduardo Gotuzzo⁹  Michael Talledo⁵  Carolina Alvarez⁵  Giovanni López⁵  Ramon Kruschewsky⁸  Saul V Schnitman³  Ricardo Khouri³  David Brassat⁴  Daniele Decanine³  Soraya Maria Menezes¹ 

[1] Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium;LASP, CPqGM-FIOCRUZ, Salvador-Bahia, Brazil;LIMI, Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation (FIOCRUZ), Rua Waldemar Falcão 121, 40296-710 Salvador-Bahia, Brazil;INSERM UMR1043 and Pôle des Neurosciences, Hôpital Purpan, Université de Toulouse, Toulouse, France;Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru;Institute for Immunological Investigation (iii-INCT), São Paulo, Brazil;Instituto de Higiene e Medicina Tropical, Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia, Universidade Nova de Lisboa, Lisbon, Portugal;Bahiana School of Medicine and Public Health, Salvador-Bahia, Brazil;Departamento de Medicina, Facultad de Medicina Alberto Hurtado, Universidad Peruana Cayetano Heredia, Lima, Peru

关键词: Gender;    Disease severity;    Ex vivo;    Human;    CD86;    Costimulatory CD80;    B cell;    Interferon-alpha/beta;    Multiple sclerosis;    HTLV-1;    Neuroinflammatory disease;   

Others  :  825763
DOI  :  10.1186/1742-2094-11-18

 received in 2013-07-15, accepted in 2014-01-13,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Menezes et al.; licensee BioMed Central Ltd.

【 图 表 】

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