Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Fc Receptor-Targeting Biologics

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, swelling, and pain in the joints and involves systemic complications. Mouse models of RA have been extensively used to model the pathogenesis of RA and to develop effective therapies. Although many components of the immune system have been studied in these models, the role of crystallizable fragment (Fc) gamma receptors (Fc gamma Rs) in RA has been sorely neglected. The aim of this review was to introduce the different mouse models of RA and to describe the different drug development strategies that have been tested in these models to target Fc gamma R function, with the focus being on drugs that have been made from the Fc of immunoglobulin G (IgG). Summary: Evidence suggests that Fc gamma Rs play a major role in immune complex-induced inflammation in autoimmune diseases, such as RA. However, there is limited knowledge on the importance of Fc gamma Rs in the human disease even though there has been extensive work in mouse models of RA. Numerous mouse models of RA are available, with each model depicting certain aspects of the disease. Induced models of RA have nonspecific immune activation with cartilage-directed autoimmunity, whereas spontaneous models of RA develop without immunization, which results in a more chronic form of arthritis. These models have been used to test Fc gamma R-targeting monoclonal antibodies, intravenous immunoglobulin (IVIg), subcutaneously administered IVIg, and recombinant Fcs for their ability to interact with and modify Fc gamma R function. Recombinant Fcs avidly bind Fc gamma Rs and exhibit enhanced therapeutic efficacy in mouse models of RA. Key Message: The therapeutic utility of targeting Fc gamma Rs with recombinant Fcs is great and should be explored in human clinical trials for autoimmune diseases, such as RA.