The autoimmune response as a potential target for tolerance induction before the development of rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory disease that affects the synovial joints. Although treatment options and efficacy have increased substantially in the past two decades, the disease cannot be cured or prevented. Therefore, rheumatoid arthritis still has a considerable effect on the quality of life of patients, not only because life-long medication is often required, but also because residual disease activity leads to progressive loss of function in the musculoskeletal system and extra-articular morbidity. Key future goals in the management of rheumatoid arthritis are the ability to induce long-lasting drug-free remission in patients with the disease (ie, to achieve a cure), and to prevent disease before it emerges. To reach these goals, it is pivotal to understand the autoimmune response underlying rheumatoid arthritis pathogenesis and to develop ways to permanently silence it (ie, to induce tolerance). For preventive studies, the identification of markers (clinical, immunological, and biological) predictive of future disease is crucial, as prevention of disease will not be feasible without the ability to identify relevant at-risk target populations. In this Series paper, we review the autoimmune response underlying rheumatoid arthritis, how rheumatoid arthritis-specific autoimmunity develops and evolves during the transition from health to disease, and how tolerance studies could be designed to achieve prevention or cure of the disease.