Mechanisms of autoimmunity in human diseases: a critical review of current dogma

Purpose of reviewAutoimmune diseases such as rheumatoid arthritis (RA) pose an increasing, worldwide economic and health burden. Significantly, no cure exists for the majority of autoimmune diseases and consequently treatment is largely aimed at controlling disease symptoms. Therefore, there exists a critical need to develop new approaches that directly address the cause of disease, leading to disease remission and ultimately cure.Recent findingsThe organs, cells and molecules involved in the breach of self-tolerance have been partially defined in experimental models of autoimmunity. However, the broad applicability of this dogma in clinical disease is only partially understood. This gap between analyses of established disease and investigating early disease pathogenesis argues for the need for complementary studies in mice and humans.SummaryThrough a combination of clinical and experimental systems, novel autoantigens and neoepitopes involved in RA have been revealed. These have clear utility in predisease diagnosis and offer the possibility of antigen-specific immunotherapy. Ongoing experimental and clinical studies, for example using dendritic cell transfer, will facilitate a clearer understanding of the molecules, cells and organs that should be targeted to reinstate immunological tolerance. Antigen-specific immunotherapy therefore offers disease intervention without broad immunosuppression, and most importantly increases the likelihood of achieving true disease remission and cure.