オカモト　ユウコ   岡本　祐子    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction.
掲載誌名	正式名：Nature reviews. Rheumatology 略　 称：Nat Rev Rheumatol ISSNコード：(1759-4804)1759-4790(Linking)
掲載区分	国外
巻・号・頁	14(9),pp.542-557
著者・共著者	Holers V Michael, Demoruelle M Kristen, Kuhn Kristine A, Buckner Jane H, Robinson William H, Okamoto Yuko, Norris Jill M, Deane Kevin D
発行年月	2018/09
概要	Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can be identified for translational research and disease prevention studies through the presence of highly informative and predictive patterns of RA-related autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the serum. In serologically positive individuals without arthritis, designated ACPA positive at risk, the presence of mucosal inflammatory processes associated with the presence of local ACPA production has been demonstrated. In other at-risk populations, local RA-related autoantibody production is present even in the absence of serum autoantibodies. Additionally, a proportion of at-risk individuals exhibit local mucosal ACPA production in the lung, as well as radiographic small-airway disease, sputum hypercellularity and increased neutrophil extracellular trap formation. Other mucosal sites in at-risk individuals also exhibit autoantibody production, inflammation and/or evidence of dysbiosis. As the proportion of individuals who exhibit such localized inflammation-associated ACPA production is substantially higher than the likelihood of an individual developing future RA, this finding raises the hypothesis that mucosal ACPAs have biologically relevant protective roles. Identifying the mechanisms that drive both the generation and loss of externally focused mucosal ACPA production and promote systemic autoantibody expression and ultimately arthritis development should provide insights into new therapeutic approaches to prevent RA.
DOI	10.1038/s41584-018-0070-0
PMID	30111803