B cell-targeted therapy in autoimmune disease: rationale, mechanisms, and clinical application.
B cells play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other autoimmune diseases. Recently, a number of biologic agents that target B cells have been tested as therapies for these conditions. These agents either deplete B cells, by targeting cell-surface antigens such as CD20, or block B cell function, for example by inhibiting the activity of B cell survival factors such as BLyS. Of this group of agents, the first in clinical use has been rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen. Initially introduced as a treatment for non-Hodgkin's lymphoma, rituximab is now approved for the treatment of RA. In this review we explore the rationale behind B cell-targeted therapy, highlight the results of clinical trials with rituximab in RA and other autoimmune diseases, and describe other emerging therapies directed at B cells.
Mease
Philip J
PJ
Seattle Rheumatology Associates, Seattle, Washington 98104, USA. pmease@nwlink.com
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007155:Immunologic Factors; D000069283:Rituximab