{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:47:36Z","timestamp":1791859656239,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AR-048592"],"award-info":[{"award-number":["AR-048592"]}]},{"name":"NIH","award":["AI-073174"],"award-info":[{"award-number":["AI-073174"]}]},{"name":"NIH","award":["AI-074948"],"award-info":[{"award-number":["AI-074948"]}]},{"name":"NIH","award":["AI-076475"],"award-info":[{"award-number":["AI-076475"]}]},{"name":"NIH","award":["AR-059351"],"award-info":[{"award-number":["AR-059351"]}]},{"name":"Nebraska Medical Center and the University of Nebraska Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Anti\u2013citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and whether <jats:italic>Porphyromonas gingivalis<\/jats:italic> facilitates the generation of ACPAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a single\u2010cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts from 7 RA patients and 4 healthy controls, respectively. Antibody reactivity with citrullinated antigens was tested by a second\u2010generation anti\u2013cyclic citrullinated peptide (anti\u2010CCP) kit and by enzyme\u2010linked immunosorbent assays (ELISAs) against citrullinated human antigens. Antibody reactivity with <jats:italic>P gingivalis<\/jats:italic> was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from <jats:italic>P gingivalis<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Approximately 19.5% of plasmablast\u2010derived antibodies from anti\u2010CCP\u2013positive RA patients, but none from 1 anti\u2010CCP\u2013negative RA patient or the healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated, with increased ratios of replacement mutations to silent mutations, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross\u2010reacted with OMAs and\/or citrullinated enolase from <jats:italic>P gingivalis<\/jats:italic>. The reactivity of ACPAs against citrullinated proteins from <jats:italic>P gingivalis<\/jats:italic> was confirmed by immunoblotting and mass spectrometry. Furthermore, some germline\u2010reverted ACPAs retained their reactivity with <jats:italic>P gingivalis<\/jats:italic> antigens but completely lost their reactivity with citrullinated human antigens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that circulating plasmablasts in RA patients produce ACPAs and that this process may be facilitated by anti\u2013<jats:italic>P gingivalis<\/jats:italic> immune responses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39455","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T16:01:59Z","timestamp":1445011319000},"page":"614-626","source":"Crossref","is-referenced-by-count":61,"title":["Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and <i>Porphyromonas gingivalis<\/i> in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"68","author":[{"given":"Song","family":"Li","sequence":"first","affiliation":[{"name":"Qilu Hospital of Shandong University, Ji'nan, Shandong, China, and University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangsheng","family":"Yu","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinshi","family":"Yue","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Liao","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqin","family":"Xie","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Thai","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[{"name":"Veterans Affairs Nebraska\u2013Western Iowa Health Care System, and University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey M.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Veterans Affairs Nebraska\u2013Western Iowa Health Care System, and University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Duryee","sequence":"additional","affiliation":[{"name":"Veterans Affairs Nebraska\u2013Western Iowa Health Care System, and University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan","family":"Sayles","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center 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