{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:58:30Z","timestamp":1784192310129,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,18]],"date-time":"2018-02-18T00:00:00Z","timestamp":1518912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32\u2010LM\u2010012417"],"award-info":[{"award-number":["T32\u2010LM\u2010012417"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001127","name":"Genentech Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001127","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008069","name":"University of California, San Francisco","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Epigenetic modifications have previously been associated with rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). In this study, we aimed to determine whether differential <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and\/or anti\u2010cyclic citrullinated protein). Fluorescence\u2010activated cell sorting was used to separate the cells into 4 immune cell subpopulations (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14+ monocytes, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19+ B cells, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4+ naive T cells, and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4+ memory T cells) per individual, and 229 epigenome\u2010wide <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2E1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">DUSP<\/jats:styled-content>22<\/jats:italic> gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type\u2013specific. Evidence of independent effects on <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation from smoking, medication use, and disease duration were also identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Methylation signatures specific to <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40408","type":"journal-article","created":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T18:06:39Z","timestamp":1514570799000},"page":"528-536","source":"Crossref","is-referenced-by-count":48,"title":["Hypomethylation of <scp>CYP<\/scp>2E1 and <scp>DUSP<\/scp>22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis 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