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This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA, and an \u201cat\u2010risk\u201d status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA. With the goal of developing RA prevention strategies, studies have characterized immune phenotypes of preclinical RA\/at\u2010risk states. From these studies, a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production, which should normally be transient, but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations, ultimately driving the development of clinically identified joint inflammation. This model can be envisioned as the progression of disease development through serial \u201ccheckpoints\u201d that in principle should constrain or resolve autoimmunity; however, instead, the checkpoints \u201cfail\u201d and clinical RA develops. Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay, diminish, halt, or even reverse the progression to clinical RA. Notably, these prevention strategies could utilize existing therapies approved for clinical RA, therapies approved for other diseases that target relevant pathways in the preclinical\/at\u2010risk state, or approaches that target novel pathways.<\/jats:p>","DOI":"10.1002\/rai2.12043","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T09:18:46Z","timestamp":1655284726000},"page":"109-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Mechanism\u2010driven strategies for prevention of rheumatoid arthritis"],"prefix":"10.1002","volume":"2","author":[{"given":"V. 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Rheumatology Stanford University Stanford California USA"},{"name":"Department of Medicine, Division of Rheumatology VA Palo Alto Health Care System Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane H.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Colorado School of Medicine Aurora Colorado 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