B-Zell-gerichtete Multiple-Sklerose-Therapie

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease of the CNS and a leading cause of lasting neurological disability in younger adults. In the last decade our knowledge of its immunopathogenesis expanded vastly. It is now widely appreciated that B cells are key players in the autoreactive immune network. They exert far more functions than merely being the precursors of antibody-producing plasma cells. B cells act as efficient antigen-presenting cells and may stimulate an autoreactive immune response through secretion of proinflammatory cytokines. It is thus only logical to test therapeutic strategies targeting B cells in MS. Rituximab is a depleting chimeric monoclonal antibody directed against CD20 and expressed on developing, naïve, and memory B cells but not stem or plasma cells. Several smaller studies have been conducted that led to a placebo controlled, double blind phase II study on efficacy which was reported recently. The results are very promising, meeting not only the primary endpoint of reduction of the surrogate MRI marker of contrast-enhancing lesions but also showing a reduction in clinical relapse rate of patients treated with rituximab. This review discusses the role of autoreactive B cells in the context of MS, analyzes the B-cell-depleting treatment studies reported, and provides information on planned and future B-cell-directed therapeutic strategies in MS.

Die Relevanz einer B-Zell-abhängigen Immunpathologie für die Multiple Sklerose

“…Tagen[90]) und lang anhaltend (bis zu 6 -9 Monate[91]) zu eliminieren. Rituximab vermittelt dabei durch Komplementaktivierung die Lyse der CD 20 + -Zellen[90], wobei sowohl zirkulierende als auch im Liquor ansässige B-Lymphozyten betroffen sind.…”