Therapeutic targeting of B lymphocyte stimulator (BLyS) in the rheumatic diseases.
B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression of BLyS in mice can lead to clinical and serological features of systemic lupus erythematosus (SLE) and Sjögren'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 rheumatic diseases, including SLE, rheumatoid arthritis (RA), Sjögren's syndrome, scleroderma, Wegener's granulomatosis, and ANCA-associated vasculitis. Results from phase-II clinical trials with a BLyS antagonist in human SLE and RA have shown the antagonist to have biological and clinical activity along with a favorable safety profile. These features collectively point to BLyS as an attractive therapeutic target in human rheumatic diseases.
Stohl
William
W
Division of Rheumatology, University of Southern California, 2011 Zonal Ave. HMR 711, Los Angeles, CA 90033, USA. stohl@usc.edu
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D012216:Rheumatic Diseases / Q000188:drug therapy*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000502:physiology
D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; C120197:BLyS receptor; D018124:Receptors, Tumor Necrosis Factor; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13