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Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

Gregory D Middleton

Rheumatoid arthritis is a common, well studied autoimmune disease characterized by a loss of self-tolerance. Current therapies have significantly advanced the successful treatment of the disease, but have been unsuccessful for a large number of patients. Furthermore, they have failed to induce long term medication free remission because they target a consequence of the disease, not the origins of a dis-regulated immune system. Current research is now focused on finding ways to correct and restore the balance of the immune system rather than just suppress it. The scientific foundations for a number of potential approaches to restoring immune tolerance already have been laid. This paper reviews a number of proposed targets for immunotherapy including vaccinations, shifting from Th1 to Th2 responses, molecules that promote the resolution of inflammation, tolerogenic dendritic cells, mesenchymal stem cells, and T regulatory cells. These strategies will hopefully allow a closer approach to a “cure” for this potentially devastating disease.