{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:23:05Z","timestamp":1791141785911,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T00:00:00Z","timestamp":1261958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Autoantibodies to citrullinated proteins are specific for rheumatoid arthritis (RA) and recognize epitopes centered by citrulline, a posttranslationally modified form of arginine. Peptidyl arginine deiminase type 4 (PAD\u20104), the enzyme that converts arginine into citrulline, is in itself a target for RA\u2010specific autoantibodies. This study was undertaken to assess whether anti\u2013PAD\u20104 autoantibodies interfere with citrullination in vitro in patients with RA, and to identify peptide targets of anti\u2013PAD\u20104 antibodies that can activate or inhibit citrullination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test whether autoantibodies to PAD\u20104 influence citrullination, an in\u2010house citrullination assay was developed using purified autoantibodies to PAD\u20104. To map B cell epitopes on PAD\u20104, 65 overlapping 20\u2010mer peptides encompassing the entire PAD\u20104 were analyzed for their reactivity in RA sera.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Autoantibodies to PAD\u20104 inhibited PAD\u20104\u2013mediated citrullination. Three linear peptides on PAD\u20104 were recognized almost uniquely by PAD\u20104 autoantibodies in the sera of patients with RA. One peptide was located in the N\u2010terminal, calcium\u2010binding domain of PAD\u20104, while 2 other peptides were located in the C\u2010terminal, substrate\u2010binding domain of PAD\u20104.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Autoantibodies to PAD\u20104 inhibit in vitro citrullination of fibrinogen by PAD\u20104. Most anti\u2013PAD\u20104\u2013positive sera recognize peptides located both in the N\u2010terminal domain (211\u2013290) and the C\u2010terminal domain (601\u2013650) of PAD\u20104.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27230","type":"journal-article","created":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T21:05:56Z","timestamp":1262034356000},"page":"126-131","source":"Crossref","is-referenced-by-count":50,"title":["Rheumatoid arthritis\u2013specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogen"],"prefix":"10.1002","volume":"62","author":[{"given":"Isabelle","family":"Auger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Balandraud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Roudier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,12,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a072958"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116713"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.1.585"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1149"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4177"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1422.034"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1206"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel023"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh614"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.033548"},{"key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/03009740510026346-1","article-title":"Peptidylarginine deiminase 4 (PADI4) identified as a conformation\u2010dependent autoantigen in rheumatoid arthritis","volume":"3","author":"Takizawa Y","year":"2005","journal-title":"Scand J Rheumatol"},{"key":"e_1_2_6_13_2","first-page":"12","article-title":"Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis: new pathways to epitope spreading","volume":"1","author":"Roth EB","year":"2006","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.080267"},{"key":"e_1_2_6_15_2","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 Rheumatol"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.096917"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.067231"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509639103"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb799"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23596"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.27230","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.27230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T15:13:33Z","timestamp":1700752413000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.27230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,28]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,1]]}},"alternative-id":["10.1002\/art.27230"],"URL":"https:\/\/doi.org\/10.1002\/art.27230","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,28]]}}}