Evolution of autoantibody responses in individuals at risk of rheumatoid arthritis

Autoantibodies such as rheumatoid factors (RFs), anti-citrullinated protein antibodies (ACPAs), and other anti-modified protein antibodies are important risk factors for the development of rheumatoid arthritis (RA) and probably play an important role in its pathogenesis. In the phase before clinical arthritis becomes apparent, different autoantibody responses can evolve because of increases in their level, isotype switching, affinity maturation, epitope spreading, and a changing glycosylation profile. This evolution may be crucial for the pathogenic properties of the autoantibody responses, and interfering with this process in individuals at risk may become a route to prevent RA. Recent data suggest that interactions between RFs and ACPAs further amplify their inflammatory potential.