Autoantigens in rheumatoid arthritis and the potential for antigen-specific tolerising immunotherapy

Summary Autoimmune diseases, including rheumatoid arthritis, develop and persist due to impaired immune self-tolerance, which has evolved to regulate inflammatory responses to injury or infection. After diagnosis, patients rarely achieve drug-free remission, and although at-risk individuals can be identified with genotyping, antibody tests, and symptoms, rheumatoid arthritis cannot yet be successfully prevented. Precision medicine is increasingly offering solutions to diseases that were previously considered to be incurable, and immunotherapy has begun to achieve this aim in cancer. Comparatively, modulating autoantigen-specific immune responses with immunotherapy for the cure of autoimmune diseases is at a relatively immature stage. Current treatments using non-specific immune or inflammatory suppression increase susceptibility to infection, and are rarely curative. However, early stage clinical trials suggesting that immunotherapy might allow extended duration of remission and even prevention of progression to disease suggest modulating tolerance in rheumatoid arthritis could be a promising opportunity for therapy.