{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:41:06Z","timestamp":1747186866687,"version":"3.40.5"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Our previous studies demonstrated that 2\u2010octynoic acid (2OA) might alter the conformational structure of the inner lipoic acid (LA) binding domain (ILD) in the E2 subunit of pyruvate dehydrogenase complex (PDC\u2010E2), leading to the loss of immune tolerance in simple primary biliary cholangitis (S\u2010PBC). Here, we further explore if this etiological mechanism also accounts for connective tissue disease\u2010associated PBC (CTD\u2010PBC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Intein\u2010mediated protein ligation was used to prepare ILD, LA\u2010ILD and 2OA\u2010ILD, and their reactivity with serum samples from 124\u2009S\u2010PBC and 132 CTD\u2010PBC patients was examined. The antibodies to LA, 2OA, LA\u2010ILD and 2OA\u2010ILD, the isotypes of antibodies to LA, 2OA and ILD, were comparatively detected between the two patient groups by enzyme\u2010linked immunosorbent assay and immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both the percentage and reactivity of antibody to 2OA in S\u2010PBC were significantly higher than in CTD\u2010PBC. Antibodies to 2OA and to LA between the two groups separately shared the same characteristics. Remarkably, coexistence of the antibodies to LA\u2010ILD and to 2OA, and coexistence of the antibodies to LA and to 2OA in S\u2010PBC were both significantly more frequent than in CTD\u2010PBC, whereas the percentage of anti\u2010LA antibody without anti\u20102OA antibody in S\u2010PBC was markedly lower than in CTD\u2010PBC. Moreover, the isotype of antibody to LA was predominantly IgG in CTD\u2010PBC, whilst this isotype was mainly IgM in S\u2010PBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Xenobiotic 2OA might play less important pathogenic role in CTD\u2010PBC than in S\u2010PBC, suggesting that different underlying mechanisms are involved in their immune intolerance to PDC\u2010E2.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15360","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T08:02:42Z","timestamp":1657094562000},"page":"2204-2215","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential immune response to xenobiotic\u2010modified self\u2010molecule in simple and connective tissue disease\u2010associated primary biliary cholangitis"],"prefix":"10.1111","volume":"42","author":[{"given":"Shangqing","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinyao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-0390","authenticated-orcid":false,"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tihong","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Division of Rheumatology, Allergy and Clinical Immunology University of California Davis School of Medicine  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Anhui University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick S. C.","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology University of California Davis School of Medicine  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5708-6509","authenticated-orcid":false,"given":"Zongwen","family":"Shuai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.01.42"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)04410-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2016.1164038"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301092"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2007.02.003"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2011.06.001"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2006.06.002"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29059"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2018.10.014"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl16365"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317993"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.01.041"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210571"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34473"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204424"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22390"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.961"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70375-0"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.02.011"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2019.109260"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26157"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000480"},{"key":"e_1_2_12_24_1","first-page":"49","article-title":"Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches","volume":"8","author":"Galoosian A","year":"2020","journal-title":"J Clin Transl Hepatol"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13448"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajg.2021.05.006"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5874"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)81373-G"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3720"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.11.001"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6346(01)00129-2"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27313"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad3439"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.007"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80281-X"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.04.009"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.01.008"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2020.10.003"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9092687"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2009.00762.x"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2019.07.001"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00522-w"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb06036.x"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.3.875"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400523"},{"key":"e_1_2_12_46_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.4049\/jimmunol.160.1.502","article-title":"A model of peptide\u2010induced lupus autoimmune B cell epitope spreading is strain specific and is not H\u20102 restricted in mice","volume":"160","author":"James JA","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2020001"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.01.003"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2407"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.052305.091720"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15360","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.15360","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15360","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T13:06:37Z","timestamp":1692623197000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,25]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/liv.15360"],"URL":"https:\/\/doi.org\/10.1111\/liv.15360","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"type":"print","value":"1478-3223"},{"type":"electronic","value":"1478-3231"}],"subject":[],"published":{"date-parts":[[2022,7,25]]},"assertion":[{"value":"2022-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}