Mucosa Biology and the Development of Rheumatoid Arthritis: Potential for Prevention by Targeting Mucosal Processes

As the goal in rheumatoid arthritis (RA) management shifts toward the prevention of joint disease, it is important to consider the role of mucosal sites in the pathogenesis of RA because they may be potential targets for preventive interventions. Multiple mucosal sites demonstrate immune dysregulation and inflammation in individuals with classifiable RA as well as, importantly, in individuals with systemic autoimmunity related to RA. The lung, gingival, and gastrointestinal mucosae are most strongly implicated in RA pathogenesis and may be sites where autoimmunity in RA initially develops. Targeting the exact site where the initial immune dysregulation in RA occurs is an appealing approach to prevention because it could avoid unwanted side effects of systemic therapies. However, several challenges must be addressed before mucosa-targeted interventions are a readily available option for RA prevention. Studies are needed to determine whether all RA-related immune dysregulation at mucosal sites will progress to joint disease and whether one or multiple mucosal sites demonstrate dysregulation prior to the development of classifiable RA. These areas of future research are likely to provide crucial pieces in the understanding of RA pathogenesis and ultimately RA prevention.