{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:29:11Z","timestamp":1787596151124,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T00:00:00Z","timestamp":1537142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2014DFA31850"],"award-info":[{"award-number":["2014DFA31850"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30971347"],"award-info":[{"award-number":["30971347"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370488"],"award-info":[{"award-number":["81370488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sera anti\u2010enteric neuronal antibodies (AENA), neuronal inflammation, and degeneration in myenteric plexus in patients with irritable bowel syndrome (IBS) were reported. Effects of sera AENA in patients with IBS are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with IBS met Rome III criteria were enrolled. Controls included healthy subjects (HS) and patients with slow transit functional constipation, inflammatory bowel disease, chronic intestinal pseudo\u2010obstruction, and autoimmune diseases. Indirect immunofluorescence was used to detect AENA. Anti\u2010enteric neuronal antibodies intensities were termed as \u201c1\u201d\u00a0=\u00a0weak fluorescence (mild positive); \u201c2\u201d\u00a0=\u00a0moderate fluorescence (moderate positive); \u201c3\u201d\u00a0=\u00a0very high fluorescence (intensive positive). Intensities of \u22651 were defined as positive and \u22652 were defined as obvious positive. Cultured myenteric neurons of small intestine from guinea pigs and human SH\u2010Sy5Y cells were incubated with fetal bovine serum (FBS), HS sera, or IBS sera with or without AENA. Indirect immunofluorescence with anti\u2010PGP9.5\/DAPI\/anti\u2010active caspase\u20103 or TUNEL, Western blot, and flow cytometry were used to detect apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Overall, 293 patients with IBS were enrolled (41.7\u00a0\u00b1\u00a011.5\u00a0years). AENA\u2010positive and obvious positive rates in IBS were higher than HS (76.8% vs 33%; 43.7% vs 7%; all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Myenteric neurons incubated with AENA moderate or intensive positive IBS sera showed higher rates of anti\u2010active caspase\u20103 and TUNEL\u2010positive cells than HS or FBS (20%\u00a0\u00b1\u00a07.3% and 35%\u00a0\u00b1\u00a013.3% vs 4.3%\u00a0\u00b1\u00a01.5% and 0.9%\u00a0\u00b1\u00a00.4%, respectively; 6.2%\u00a0\u00b1\u00a02.0% and 10.2%\u00a0\u00b1\u00a04.6% vs 1.3%\u00a0\u00b1\u00a01.9% and 0.5%\u00b10.5%, respectively; all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Human SH\u2010Sy5Y cells incubated with AENA moderate or intensive positive IBS sera showed increased cleaved caspase\u20103 and Bax expression and decreased Bcl\u20102 expression. Flow cytometry showed apoptosis rates of these two groups were higher than that of AENA mild positive, negative, HS, and FBS (7.6%\u00b10.8% and 10.7%\u00b11.3% vs 5.0%\u00b10.8%, 3.8%\u00b10.3%, 3.4%\u00b10.2% and, 2.8%\u00b10.2%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>The AENA obvious positive rate in patients with IBS was higher than HS, and sera with higher levels of AENA promoted neuronal apoptosis. AENA\u2010mediated neuropathy might exist in a subset of patients with IBS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13457","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T06:23:44Z","timestamp":1537251824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Sera with anti\u2010enteric neuronal antibodies from patients with irritable bowel syndrome promote apoptosis in myenteric neurons of guinea pigs and human SH\u2010Sy5Y cells"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2927-9266","authenticated-orcid":false,"given":"Wenjuan","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Wexner Medical Center The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie D","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Wexner Medical Center The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-8779","authenticated-orcid":false,"given":"Xiucai","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 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