{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T23:07:08Z","timestamp":1781478428192,"version":"3.54.1"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":88,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20591167"],"award-info":[{"award-number":["20591167"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the reactivity of monoclonal anti\u2013citrullinated protein antibody (ACPA) obtained from peripheral blood B cells of rheumatoid arthritis (RA) patients with human autoantigens as well as environmental proteins by determining the essential epitope for the ACPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A human monoclonal ACPA (cyclic citrullinated peptide antibody 1 [CCP\u2010Ab1]) was obtained by screening peripheral blood lymphocytes from 31 patients with RA using a novel monoclonal antibody\u2013secreting cell (ASC) screening system, the immunospot\u2010array assay on a chip. The essential epitope for CCP\u2010Ab1 was determined using epitope mapping. Then, human, microbial, and plant proteins that share the essential epitope identified were searched using BLAST. Finally, representative proteins identified by the search were produced in vitro, and their reactivity with CCP\u2010Ab1 was examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CCP\u2010Ab1 bound CCP in a citrulline\u2010indispensable manner. In CCP, the 6 amino acid residues required for CCP\u2010Ab1 binding were identified. In the BLAST search, 38 human, 56 viral, 1,383 fungal, 547 bacterial, and 1,072 plant proteins were found to share the essential epitope, and CCP\u2010Ab1 reacted with all of the recombinant citrullinated proteins tested, which included the various environmental factors, such as various plant proteins that are part of the daily diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate, for the first time, that a monoclonal ACPA (CCP\u2010Ab1) derived from RA patients cross\u2010reacts not only with various autoantigens but also with numerous plant and microbial proteins. We propose that countless environmental factors, including microbes and diet, may trigger the generation of ACPAs that then cross\u2010react with various citrullinated human autoantigens through molecular mimicry to induce RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39161","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T11:02:41Z","timestamp":1429268561000},"page":"2020-2031","source":"Crossref","is-referenced-by-count":34,"title":["Monoclonal Antibody Against Citrullinated Peptides Obtained From Rheumatoid Arthritis Patients Reacts With Numerous Citrullinated Microbial and Food Proteins"],"prefix":"10.1002","volume":"67","author":[{"given":"Reina","family":"Tsuda","sequence":"first","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiko","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Hamana","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Taki","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Tobe","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Jichi Medical University Shimotsuke Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johji","family":"Imura","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kishi","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Muraguchi","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute, Boston, Massachusetts), Hiroshi Hamana, PhD, Hirofumi Taki, MD, PhD, Kazuyuki Tobe, MD, PhD, Eiji Sugiyama, MD, PhD (current address: Hiroshima University Hospital, Hiroshima, Japan), Johji Imura, MD, PhD, Hiroyuki Kishi, PhD, Atsushi Muraguchi, MD, PhD: University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Sugitani Campus Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2010.10.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1187"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20316"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21391"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21739"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20018"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1443.013"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.76"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00850.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4177"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1149"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21629"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535790"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.25036"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.131102"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200421"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116713"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117969"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.1.585"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121486"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.322"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1966"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.06.012"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3358"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/B810438G"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20471"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20478"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112123"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh412"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.207"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1316"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1093\/clinchem\/47.6.1089","article-title":"Diagnostic accuracy of the anti\u2010citrulline antibody assay for rheumatoid arthritis [published erratum appears in","volume":"47","author":"Bizzaro N","year":"2001","journal-title":"Clin Chem"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar93"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(00)00206-4"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2471267"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-013-0185-9"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.124537"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23936"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23127"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1845"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.139"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201241"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44447"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.8.2449"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3237"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3248-3256.1999"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27552"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199907)42:7<1485::AID-ANR24>3.0.CO;2-7"},{"key":"e_1_2_7_52_1","first-page":"656","article-title":"Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs","volume":"24","author":"Moen K","year":"2006","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_53_1","article-title":"Strategies to predict rheumatoid arthritis development in at\u2010risk populations","author":"Karlson EW","year":"2014","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.126821"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.538"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39161","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:41:37Z","timestamp":1759941697000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":54,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1002\/art.39161"],"URL":"https:\/\/doi.org\/10.1002\/art.39161","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]}}}