Abstract
PURPOSE OF REVIEW: The cause of rheumatoid arthritis (RA), as well as the timing and anatomic site at which RA-related autoimmunity is initiated, is currently unknown. An improved understanding of the initial steps in the development of RA would provide insights into disease pathogenesis that could ultimately lead to more effective treatments and/or novel preventive strategies in RA. RECENT FINDINGS: Systemic inflammation and autoimmunity in RA begin long before the onset of detectable joint inflammation. Emerging data suggest that RA-related autoimmunity may be initiated at a mucosal site years before the onset of joint symptoms. The candidate sites of origin include the oral, lung and gastrointestinal mucosa, as data consistent with this hypothesis have been generated for each location. Individual patients may undergo initiation events at unique sites, but still converge on similar joint findings as the disease process evolves. SUMMARY: Investigations are needed to determine when and where RA begins, including comprehensive prospective studies of individuals in the preclinical period of RA that can provide insight into the relationship between mucosal inflammation, RA-related autoantibody generation and subsequent joint inflammation in RA.