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

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. © 2014 menezes et al.; licensee biomed central ltd.