Immunologic Mechanisms in the Pathogenesis of Rheumatoid ArthritisFirestein, Gary S. MDJCR: Journal of Clinical Rheumatology: June 2005 - Volume 11 - Issue 3 - p S39-S44 doi: 10.1097/01.rhu.0000166673.34461.33 Supplement Article Abstract Author Information Although much is known about the etiology and pathogenesis of rheumatoid arthritis (RA), our understanding of the immune pathways remains incomplete. The observed clinical and pathologic manifestations result from activation of several interrelated immune pathways. Current concepts of RA pathogenesis, supported by animal models, laboratory studies, and clinical observation, have reestablished and revised some of the original views. Early proposals emphasized the importance of autoantibodies and immune complexes in the initiation of RA, suggested a role for T cells in the inflammatory response characteristic of RA, and based disease perpetuation on an imbalance in the cytokine networks. We now recognize that each of these interrelated mechanisms significantly contributes to RA pathogenesis, including T cells that can help initiate and perpetuate the disease. This article reviews the major components and immune pathways involved in RA and briefly discusses the animal models that contribute to our understanding. Although a unified theory of RA pathogenesis may not be possible at this time, a paradigm is presented that considers the immune pathways that contribute to disease progression and joint destruction. These pathways may have important implications for treatment, because their modulation by biologic response modifiers (BRMs) directed toward specific targets provides benefits to patients with RA. BRMs are a new class of therapeutic agents derived from biologically active molecules and designed to modulate specific immune or inflammatory pathways. Although currently approved BRMs still have limitations, choosing an appropriate target, possibly early rather than late in the immune response, might result in new and improved therapies for RA. From the Department of Medicine and the Division of Rheumatology, Allergy, and Immunology, University of California, San Diego School of Medicine, La Jolla, California. Reprints: Gary S. Firestein, Professor of Medicine, Chief of Rheumatology, Allergy, and Immunology, University of California, San Diego School of Medicine, 9500 Gilman Drive BSB, Room 5098, Mail Code 0656, La Jolla, CA 92093. E-mail: email@example.com. © 2005 Lippincott Williams & Wilkins, Inc.