{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:07:56Z","timestamp":1789459676321,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK057892"],"award-info":[{"award-number":["R01 DK057892"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Olmesartan\u2010associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue\u2010like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To determine the mechanistic similarities of OAE with coeliac sprue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Duodenal biopsies were extracted from OAE patients before (<jats:italic>n<\/jats:italic> = 11) or after (<jats:italic>n<\/jats:italic> = 17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were seven \u2018on\/off\u2019 paired samples. Formalin\u2010fixed biopsies were stained for CD8, CD4, FoxP3, IL\u201015R and psmad 2\/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL\u201015, IL\u201015R and ZO\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the \u2018on olmesartan medoxomil\u2019 duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T\u2010cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco\u20102 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO\u20101, a tight junction protein, is disrupted in olmesartan medoxomil\u2010treated Caco\u20102 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Olmesartan\u2010associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effects of gluten upon the epithelium of coeliac patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13413","type":"journal-article","created":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T05:48:58Z","timestamp":1443678538000},"page":"1303-1314","source":"Crossref","is-referenced-by-count":54,"title":["Immunopathogenesis of olmesartan\u2010associated enteropathy"],"prefix":"10.1111","volume":"42","author":[{"given":"E. V.","family":"Marietta","sequence":"first","affiliation":[{"name":"Department of Immunology Mayo Clinic Rochester MN USA"},{"name":"Department of Dermatology Mayo Clinic Rochester MN USA"},{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. K.","family":"Cartee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rishi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. S.","family":"Choung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.\u2010T.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rubio\u2010Tapia","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic Rochester MN USA"},{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.06.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12937"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(14)62186-7"},{"key":"e_1_2_7_5_1","first-page":"A7370","article-title":"Diarrhoea and malabsorption due to olmesartan use","volume":"158","author":"Beurden YH","year":"2014","journal-title":"Ned Tijdschr Geneeskd"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i40.6928"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastrohep.2014.05.006"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4321\/S1130-01082014000200011"},{"key":"e_1_2_7_9_1","first-page":"494098","article-title":"Olmesartan associated sprue\u2010like enteropathy and colon perforation","volume":"2014","author":"Abdelghany M","year":"2014","journal-title":"Case Rep Gastrointest Med"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2515\/therapie\/2013057"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e31829a27e6"},{"key":"e_1_2_7_12_1","first-page":"618071","article-title":"Spruelike enteropathy associated with olmesartan: an unusual case of severe diarrhea","volume":"2013","author":"Dreifuss SE","year":"2013","journal-title":"Case Rep Gastrointest Med"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.45"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2013.12.014"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.112.007278"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-012-0276-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.06.006"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.023"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41344"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.068684"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0582"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908834106"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.1.460"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.80"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.01.003"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520500235334"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12191"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(14)62187-9"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.13413","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.13413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T19:13:46Z","timestamp":1695496426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.13413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":27,"journal-issue":{"issue":"11-12","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1111\/apt.13413"],"URL":"https:\/\/doi.org\/10.1111\/apt.13413","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10]]}}}