Bridging autoantibodies and arthritis: the role of Fc receptors.

Autoantibodies represent a hallmark of Rheumatoid arthritis (RA), which is a chronic inflammatory autoimmune disease characterized by inflammation and damage in the joints. Anti-Citrullinated Protein Antibodies (ACPA) are the most prominent autoantibodies present in RA patients. These autoantibodies have been intensively investigated during the last 20 years due to their diagnostic and predictive value. Furthermore, they are believed to be involved in mediating the damage associated with RA. Antibodies of the IgG isotype interact with the immune system via Fcγ receptors expressed on immune cells as well as nonimmune cells. These receptors, therefore, form the bridge between Fcγ receptor-positive cells and antibodies complexed to antigen allowing the modulation and activation of cellular immune responses that are involved in immune defense against invading microorganisms. However, in case triggered by antibodies against self-antigens, they can also play a pivotal role in the induction and perpetuation of autoimmune diseases such as RA. Mouse models have been indispensably important for understanding the role of Fcγ receptors in the development of arthritis. Here we discuss the contribution of autoantibodies to the pathogenesis of arthritis in preclinical animal models, as well as RA, in relation to their interaction with the different (immune inhibitory and activating) Fcγ receptors.