B cell targeted therapies in autoimmune diseases

Abstract

In addition to rheumatoid arthritis (RA), B cells are likely to play a significant role in the development of other autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE), myositis, and vasculitis. Small-vessel vasculitis subtypes may be immune complex-mediated (cryoglobulinemia) or antineutrophil cytoplasmic antibody (ANCA)-associated; ANCA may be involved in the pathogenesis of vasculitis. In SLE, both antibody-associated and antibody-independent processes are almost certainly involved. B cell activity and autoantibody production are increased, while patients often have reduced peripheral B cells and abnormal B cell profiles. B lymphocyte stimulator (BLyS) protein regulates B cell activation and differentiation. For these reasons, B cells and the molecules that activate them are potential therapeutic targets in these diseases. Recent clinical trial data from small studies of rituximab (RTX) in SLE suggest that treatment improved clinical variables and measures of disease activity in patients, including those with central nervous system SLE. With retreatment, patients whose B cells were successfully depleted continued to show improvement in clinical and laboratory variables. Preliminary data suggest that treatment with RTX may be effective in ANCA-associated vasculitis. In addition a recent study showed significant benefit with myositis. Although these studies contain small cohorts of patients, they demonstrate that B cell-modulating therapies show promise in treatment of a variety of autoimmune diseases.