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However, understanding mechanisms that dysregulate citrullination in RA has important challenges. Citrullination is a normal process in immune and non\u2010immune cells, which is likely activated by different conditions (eg, inflammation) with no pathogenic consequences. In a complex inflammatory environment such as the RA joint, unique strategies are therefore required to dissect specific mechanisms involved in the abnormal production of citrullinated proteins. Here, we will review current models of citrullination in RA and discuss critical components that, in our view, are relevant to understanding the accumulation of citrullinated proteins in the RA joint, collectively referred to as the RA citrullinome. In particular, we will focus on potential caveats in the study of citrullination in RA and will highlight methods to precisely detect citrullinated proteins in complex biological samples, which is a confirmatory approach to mechanistically link the RA citrullinome with unique pathogenic pathways in RA.<\/jats:p>","DOI":"10.1111\/imr.12834","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T05:00:07Z","timestamp":1577336407000},"page":"133-147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Insights into the study and origin of the citrullinome in rheumatoid arthritis"],"prefix":"10.1111","volume":"294","author":[{"given":"Justyna","family":"Fert\u2010Bober","sequence":"first","affiliation":[{"name":"The Smidt Heart Institute Department of Medicine Cedars\u2010Sinai Medical Center Los Angeles 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