Carbamylated histone antibodies potentiate osteoclast formation and associate with bone erosion in rheumatoid arthritis.

Rheumatoid arthritis (RA) is known to include a pre-RA stage that can be defined as the presence of familial or genetic risk factors, biomarker abnormalities (eg, anticitrullinated protein antibodies [ACPA]), symptoms, and even abnormal imaging findings prior to the development of the onset of clinical RA with inflammatory arthritis that is apparent on physical examination. Indeed, there are multiple completed or ongoing retrospective case-control as well as prospective observational studies to identify the key biologic drivers of disease. Further, building on the predictive ability of combinations of biomarkers, symptoms, and imaging for future RA, there are multiple clinical trials completed, underway, or in development to identify approaches that may prevent, delay, or ameliorate future clinical RA in at-risk individuals. Importantly, however, although an effective preventive intervention has not yet been identified, at-risk individuals are being increasingly identified in clinical care; this presents a challenge of how to manage these individuals in clinical practice. This review will discuss the current understanding of the biology and natural history of RA development, nomenclature, and current models for prediction of future RA, as well as evaluate the current and ongoing clinical prevention trials with the overall goal to provide insights into the challenges and opportunities in the field of RA prevention. Moreover, this review will provide up-to-date options for clinical management of individuals at risk for RA.

Rheumatoid Arthritis (RA) is a common autoimmune disease that targets the synovial joints leading to arthritis. Although the etiology of RA remains largely unknown, it is clear that numerous modifiable risk factors confer increased risk to developing RA. Of these risk factors, cigarette smoking, nutrition, obesity, occupational exposures and periodontal disease all incrementally increase RA risk. However, the precise immunological mechanisms by which these risk factors lead to RA are not well understood. Basic and translational studies have provided key insights into the relationship between inflammation, antibody production and the influence in other key cellular events such as T cell polarization in RA risk. Improving our general understanding of the mechanisms which lead to RA will help identify targets for prevention trials, which are underway in at-risk populations. Herein, we review the modifiable risk factors that are linked to RA development and describe immune mechanisms that may be involved. We highlight the few studies that have sought to understand if modification of these risk factors reduces RA risk. Finally, we speculate that modification of risk factors may be an appealing avenue for prevention for some at-risk individuals, specifically those who prefer lifestyle interventions due to safety and economic reasons.