Reduced type I collagen gene expression by skin fibroblasts of @entity1 with XXXX after one treatment course with rituximab.

@entity1 @entity82 @entity2225 @entity2631 @entity3820 @entity785
OBJECTIVES: There is evidence that B lymphocytes play a role in the pathogenesis of @entity785 ( @entity2631 ). Stimulatory autoantibodies targeting and activating normal @entity1 fibroblasts in vitro have been demonstrated in sera from @entity2631 @entity1 . Rituximab is a monoclonal antibody which selectively targets and depletes @entity2225 + B lymphocytes. We investigated the biological effects of rituximab in six @entity1 affected by @entity2631 with severe skin involvement. METHODS: Six @entity1 with severe skin @entity82 , unresponsive to immunosuppressive treatment, were treated with 375 mg/m2 per week of intravenous rituximab for a total of four doses. Serum stimulatory autoantibodies to the PDGF receptor were detected. Fibroblast activation was evaluated in fibroblasts grown from skin biopsies performed at baseline and at months 3 and 6 post-treatment. The modified Rodnan's skin score, health assessment questionnaire (HAQ) and visual analogic scale (VAS) for global wellness and B lymphocyte count were performed monthly. RESULTS: A significant reduction of anti-PDGF receptor autoantibodies was observed in the serum of all @entity1 3 months after treatment. Fibroblasts showed a significant downregulation of type I collagen gene expression and of the intracellular signalling triggered by anti- @entity3820 autoantibodies. A decrease of the skin score and an improvement of disability indexes matched with the in vitro results. A single course of rituximab reduced @entity2631 fibroblast activation in vitro and the serum levels of anti- @entity3820 stimulatory autoantibodies. CONCLUSIONS: These data provide further evidence of B-cell involvement in the pathogenesis of @entity2631 . Targeting B cells may be a promising treatment for @entity2631 @entity1 , and controlled clinical trials are warranted.
