Systemic Immune-Based Rheumatic Diseases: Blissless States of BLySfulness

Abstract

B lymphocyte stimulator (BLyS) is a vital B-cell survival and differentiation factor. Overexpression of BLyS in mice can lead to clinical and serological features of systemic lupus erythematosus (SLE) and Sjogren’s syndrome (SS). Treatment with BLyS antagonists of mice with established SLE ameliorates disease progression and enhances survival. Moreover, similar treatment of mice with inflammatory arthritis ameliorates the ongoing inflammation and subsequent joint destruction. In humans, BLyS overexpression is common in patients with several systemic immune-based rheumatic diseases (SIRDs), including SLE, rheumatoid arthritis (RA), SS, scleroderma, dermatomyositis, ANCA-associated vasculitis, and mixed cryoglobulinemia. Phase-I and phase-II clinical trials with BLyS antagonists in SLE and RA have documented in vivo biological activities along with favorable safety profiles for these agents and have pointed to beneficial effects in subsets of patients. These features collectively point to BLyS as an attractive therapeutic target in human SIRDs.