The role of the complement and the FcγR system in the pathogenesis of arthritis

Rheumatoid arthritis (RA) is a severe chronic disease characterized by the inflammation of synovial tissue in joints, which causes pain and dysfunction and ultimately leads to the destruction of joints. The pathogenesis of RA is not yet fully understood [1,2]. A general pathogenic hallmark of RA is the infiltration of T cells, B cells, macrophages, granulocytes and particular neutrophils into the synovial lining and fluid and the periarticular spaces. These infiltrating cells produce abundant cytokines, dominated mainly by the inflammatory type of cytokines such as tumor necrosis factor (TNF-α) and IL-1, which further activate effector cells such as macrophages and synoviocytes, finally leading to the damage of joint tissue. The occurrence of elevated levels of rheumatoid factors (RFs), which are autoantibodies against the Fc portion of IgG molecules, are a diagnostic marker for RA, even though they are not specific for the disease. RF is present not only in patients with RA but also in patients with other autoimmune diseases or healthy donors. The role of RF in the pathogenesis of RA, or even whether it has one, is still not clear [3].More recently, autoantibodies against citrullinated proteins have been shown to be specifically present in patients with RA [4]. Studies involving animal models have shed more light on the role of autoantibodies in the pathogenesis of the disease [5,6]. There has been increasing evidence of the importance of autoantibodies and innate immunity cellular factors (Fc receptors and components of the complement system) in the pathophysiology of immunological diseases. In collagen-induced arthritis (CIA) [7], a model in which arthritis is induced in certain susceptible mouse strains by injecting collagen type II (CII) in complete Freund's adjuvant, the antibodies directed to CII epitopes exposed on the cartilage surface in the joints have a crucial role in pathogenesis [8,9].In a more recent mouse model of arthritis known as the K/B × N mode