Towards prevention of autoimmune diseases: The example of rheumatoid arthritis.

Prevention is the ultimate aim for clinicians and scientists concerned with severe diseases, like many immune-mediated conditions. Here, we describe recent progress in the understanding of etiology and molecular pathogenesis of rheumatoid arthritis (RA), which make this disease a potential prototype for prevention that may include both public health measures and targeted and personalized approaches that we call "personalized prevention." Critical components of this knowledge are (i) better understanding of the dynamics of the RA-associated autoimmunity that may begin many years before onset of joint inflammation; (ii) insights into how this immunity may be triggered at mucosal surfaces after distinct environmental challenges; (iii) better understanding of which features of the pre-existing immunity may cause symptoms that precede joint inflammation and predict a high risk for imminent arthritis development; and (iv) how molecular events occurring before onset of inflammation might be targeted by existing or future therapies, ultimately by specific targeting of Major histocompatibility complex (MHC) class II restricted and RA-specific immunity. Our main conclusion is that studies and interventions in the phase of autoimmunity preceding RA offer new opportunities to prevent the disease and thereby also understand the molecular pathogenesis of its different variants.