{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:46:52Z","timestamp":1785322012147,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","award":["Innovative Research Award"],"award-info":[{"award-number":["Innovative Research Award"]}],"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":["R01 AR050026"],"award-info":[{"award-number":["R01 AR050026"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR069569"],"award-info":[{"award-number":["R01 AR069569"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10 OD021844"],"award-info":[{"award-number":["S10 OD021844"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Citrullinated proteins are hallmark targets of autoantibodies in rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). Our study was undertaken to determine the effect of autocitrullination on the recognition of peptidylarginine deiminases (<jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>s) 2 and 4 by autoantibodies in <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Autocitrullination sites in <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>4 were determined by mass spectrometry and literature review. Antibodies against native and autocitrullinated <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>s in 184 patients with <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> were detected by enzyme\u2010linked immunosorbent assay. Linear regression analysis, outlier calculations, and competition assays were performed to evaluate antibody reactivity to native and citrullinated <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Autocitrullination of <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>4 was detected in 16 (48%) of 33 arginine residues and 7 (26%) of 27 arginine residues, respectively. Despite robust autocitrullination, autoantibodies bound similarly to native and citrullinated <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>2 or <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>4 (\u03c1 = 0.927 and \u03c1 = 0.903, respectively; each <jats:italic>P<\/jats:italic> &lt; 0.0001). Although subsets of anti\u2010<jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>\u2013positive sera were identified as exhibiting preferential recognition of native or citrullinated <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>2 (40.5% or 4.8%, respectively) or <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>4 (11.7% or 10.4%, respectively), competition assays confirmed that the majority of anti\u2010<jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content> reactivity was attributed to a pool of autoantibodies that bound irrespective of citrullination status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Autocitrullination does not affect autoantibody reactivity to <jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content>s in the majority of patients with <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>, demonstrating that anti\u2010<jats:styled-content style=\"fixed-case\">PAD<\/jats:styled-content> antibodies are distinct from anti\u2013citrullinated protein antibodies in their dependence on citrullination for binding.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41276","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T09:38:25Z","timestamp":1586252305000},"page":"1476-1482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Citrulline Not a Major Determinant in the Recognition of Peptidylarginine Deiminase 2 and 4 by Autoantibodies in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-0279","authenticated-orcid":false,"given":"Erika","family":"Darrah","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan L.","family":"Davis","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7735-0437","authenticated-orcid":false,"given":"Ashley M.","family":"Curran","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Naik","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Hyun","family":"Na","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-0402","authenticated-orcid":false,"given":"Jon T.","family":"Giles","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians and Surgeons  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3415-0704","authenticated-orcid":false,"given":"Felipe","family":"Andrade","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000452"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23618"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081259"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1206"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02696"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23596"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.080267"},{"key":"e_1_2_7_9_1","first-page":"969","article-title":"Prevalence and significance of anti\u2010peptidylarginine deiminase 4 antibodies in rheumatoid arthritis","volume":"35","author":"Zhao J","year":"2008","journal-title":"J 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