ABSTRACT
Rheumatoid arthritis (RA) is a systemic, chronic in–ammatory disease that is manifested as a destructive polyarthritis in association with serological evidence of autoreactivity. It is characterized by chronic pain and joint destruction, premature mortality, and elevated risk of disability, with high costs for those suffering from this disease and for the society. It affects up to 0.5%–1% of the world’s population, with a male-to-female ratio of 3:1, and is the most common in–ammatory joint disease. The onset of disease can occur at any age; however, the prevalence increases with age and the peak incidence is between the fourth and the sixth decade (Abdel-Nasser et al., 1997). Clinically, RA is symmetrical polyarticular arthritis marked by chronic systemic in–ammation, synovial in—ltrates, and progressive cell-mediated destruction of the joints and their adjacent chronic in–ammation of the synovium along with various clinical features of a systemic disease. The disease is characterized by persistent and progressive synovitis of peripheral joints, leading to destruction of cartilage and subchondral bone. The pathogenic basis of RA is a sustained speci—c immune response against yet unknown self-antigens. It is believed that in RA, the persistent autoimmune response mediates local synovial in–ammation and cellular in—ltration, which ultimately result in tissue damage. The two main pathophysiologic events leading to RA are (1) hyperplastic synovial lining cells, the layer in direct contact with the intra-articular cavity, and (2) mononuclear cell in—ltration in the subintimal layer. The hyperplastic lining is composed of macrophage-like type I synoviocyte and —broblastlike type II synoviocyte. Many cell groups exist in the in—ltrate of the subintimal synovial layer, including T cells, B cells, dendritic cells (DCs), macrophages, —broblasts, granulocytes, and mast cells. Another major pathological phenomenon in RA is the formation of a destructive type of tissue that invades at the interface between cartilage and bone and is known as pannus. Pannus formation
Introduction ...................................................................................................................................... 55 T Cells in RA ................................................................................................................................... 56 B Cells and Autoantibody ................................................................................................................60 Cytokines in RA ............................................................................................................................... 62
Proin–ammatory Cytokines .................................................................................................... 62 Anti-in–ammatory Cytokines .................................................................................................64 Chemokines (Chemotactic Cytokines) ...................................................................................64
