{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:13:46Z","timestamp":1790784826421,"version":"4.1.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["275053"],"award-info":[{"award-number":["275053"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["ERC-2010-Ad-268541"],"award-info":[{"award-number":["ERC-2010-Ad-268541"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005366","name":"Universitetet i Oslo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Celiac disease is an autoimmune enteropathy driven by dietary intake of gluten proteins. Typical histopathologic features are villous flattening, crypt hyperplasia and infiltration of inflammatory cells in the intestinal epithelium and lamina propria. The disease is hallmarked by the gluten-dependent production of autoantibodies targeting the enzyme transglutaminase 2 (TG2). While these antibodies are specific and sensitive diagnostic markers of the disease, a role in the development of the enteropathy has never been established.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We addressed this question by injecting murine antibodies harboring the variable domains of a prototypic celiac anti-TG2 immunoglobulin into TG2-sufficient and TG2-deficient mice evaluating for celiac enteropathy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We found no histopathologic abnormalities nor clinical signs of disease related to the injection of anti-TG2 IgG or IgA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings do not support a direct role for secreted anti-TG2 antibodies in the development of the celiac enteropathy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0266543","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T17:43:01Z","timestamp":1649266981000},"page":"e0266543","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Injection of prototypic celiac anti-transglutaminase 2 antibodies in mice does not cause enteropathy"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4450-6970","authenticated-orcid":true,"given":"Christian B.","family":"Lindstad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Sulkanen","year":"1998","journal-title":"Gastroenterology"},{"issue":"4","key":"pone.0266543.ref006","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/MPG.0b013e31817b6dec","article-title":"Gluten-dependent small bowel mucosal transglutaminase 2-specific IgA deposits in overt and mild enteropathy coeliac disease","volume":"47","author":"O Koskinen","year":"2008","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"12","key":"pone.0266543.ref007","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1136\/gut.2005.071514","article-title":"Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits","volume":"55","author":"TT Salmi","year":"2006","journal-title":"Gut"},{"issue":"1","key":"pone.0266543.ref008","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12016-016-8557-4","article-title":"Transglutaminase 2 and transglutaminase 2 autoantibodies in celiac disease: a review","volume":"57","author":"T Rauhavirta","year":"2019","journal-title":"Clin Rev Allergy Immunol"},{"issue":"5","key":"pone.0266543.ref009","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/gut.2003.024836","article-title":"In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies","volume":"53","author":"IR Korponay-Szab\u00f3","year":"2004","journal-title":"Gut"},{"issue":"8","key":"pone.0266543.ref010","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.dld.2011.01.015","article-title":"Intestinal deposits of anti-tissue transglutaminase IgA in childhood celiac disease","volume":"43","author":"M Maglio","year":"2011","journal-title":"Dig Liver Dis"},{"issue":"2","key":"pone.0266543.ref011","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.cgh.2012.09.030","article-title":"Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease","volume":"11","author":"J Taavela","year":"2013","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"1","key":"pone.0266543.ref012","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1365-2249.2012.04673.x","article-title":"Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease","volume":"171","author":"A Tosco","year":"2013","journal-title":"Clin Exp Immunol"},{"issue":"2","key":"pone.0266543.ref013","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S1568-9972(03)00054-5","article-title":"The role of the immune response against tissue transglutaminase in the pathogenesis of coeliac disease","volume":"3","author":"T Freitag","year":"2004","journal-title":"Autoimmun Rev"},{"issue":"6","key":"pone.0266543.ref014","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.molimm.2007.09.025","article-title":"Anti-idiotypic response in mice expressing human autoantibodies","volume":"45","author":"R Di Niro","year":"2008","journal-title":"Mol 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celiac disease intestinal lesions","volume":"18","author":"R Di Niro","year":"2012","journal-title":"Nat Med"},{"issue":"2","key":"pone.0266543.ref018","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190860","article-title":"B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2","volume":"217","author":"MF du Pr\u00e9","year":"2020","journal-title":"J Exp Med"},{"issue":"1","key":"pone.0266543.ref019","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1128\/MCB.21.1.148-155.2001","article-title":"Gene disruption of tissue transglutaminase","volume":"21","author":"V De Laurenzi","year":"2001","journal-title":"Mol Cell Biol"},{"issue":"7","key":"pone.0266543.ref020","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"33","key":"pone.0266543.ref021","doi-asserted-by":"crossref","first-page":"25402","DOI":"10.1074\/jbc.M109.097162","article-title":"Redox regulation of transglutaminase 2 activity","volume":"285","author":"J Stamnaes","year":"2010","journal-title":"J Biol Chem"},{"issue":"12","key":"pone.0266543.ref022","doi-asserted-by":"crossref","first-page":"5981","DOI":"10.4049\/jimmunol.1300183","article-title":"Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells","volume":"190","author":"R Iversen","year":"2013","journal-title":"J Immunol"},{"issue":"3","key":"pone.0266543.ref023","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1136\/gut.42.3.362","article-title":"Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study. Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP) and \"Club del Tenue\" Working Groups on Coeliac Disease","volume":"42","author":"F Cataldo","year":"1998","journal-title":"Gut"},{"issue":"5","key":"pone.0266543.ref024","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3109\/00365529209000089","article-title":"Selective IgA deficiency and coeliac disease","volume":"27","author":"P Collin","year":"1992","journal-title":"Scand J Gastroenterol"},{"issue":"2","key":"pone.0266543.ref025","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/00004836-199709000-00004","article-title":"Celiac sprue and immunodeficiency states: a 25-year review","volume":"25","author":"MA Heneghan","year":"1997","journal-title":"J Clin Gastroenterol"},{"issue":"2","key":"pone.0266543.ref026","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/eji.1830180221","article-title":"The half-lives of serum immunoglobulins in adult mice","volume":"18","author":"P Vieira","year":"1988","journal-title":"Eur J Immunol"},{"issue":"5","key":"pone.0266543.ref027","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/19420862.2017.1323159","article-title":"Affinity of human IgG subclasses to mouse Fc gamma receptors","volume":"9","author":"G Dekkers","year":"2017","journal-title":"MAbs"},{"issue":"24","key":"pone.0266543.ref028","doi-asserted-by":"crossref","first-page":"5640","DOI":"10.1182\/blood-2012-01-380121","article-title":"Properties of mouse and human IgG receptors and their contribution to disease models","volume":"119","author":"P. Bruhns","year":"2012","journal-title":"Blood"},{"key":"pone.0266543.ref029","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3389\/fimmu.2018.00958","article-title":"Potential of murine IgG1 and human IgG4 to inhibit the classical complement and Fc\u03b3 receptor activation pathways","volume":"9","author":"GM Lilienthal","year":"2018","journal-title":"Front Immunol"},{"issue":"7","key":"pone.0266543.ref030","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1136\/gutjnl-2012-302196","article-title":"Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease","volume":"62","author":"D Leffler","year":"2013","journal-title":"Gut"},{"key":"pone.0266543.ref031","article-title":"Evaluating responses to gluten challenge: a randomized, double-blind, 2-dose gluten challenge trial","author":"MM Leonard","year":"2020","journal-title":"Gastroenterology"},{"issue":"9","key":"pone.0266543.ref032","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1136\/gutjnl-2017-314461","article-title":"HLA-DQ:gluten tetramer test in blood gives better detection of coeliac patients than biopsy after 14-day gluten challenge","volume":"67","author":"VK Sarna","year":"2018","journal-title":"Gut"},{"issue":"6487","key":"pone.0266543.ref033","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1126\/science.aay3037","article-title":"Autoimmunity provoked by foreign antigens","volume":"368","author":"R Iversen","year":"2020","journal-title":"Science"},{"issue":"8","key":"pone.0266543.ref034","article-title":"Autoantibodies in the extraintestinal manifestations of celiac disease","volume":"10","author":"XB Yu","year":"2018","journal-title":"Nutrients"},{"issue":"7","key":"pone.0266543.ref035","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1053\/j.gastro.2021.02.063","article-title":"B Lymphocytes Contribute to Celiac Disease Pathogenesis","volume":"160","author":"T Lejeune","year":"2021","journal-title":"Gastroenterology"},{"issue":"7796","key":"pone.0266543.ref036","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41586-020-2003-8","article-title":"IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease","volume":"578","author":"V Abadie","year":"2020","journal-title":"Nature"},{"issue":"1","key":"pone.0266543.ref037","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1056\/NEJMoa2032441","article-title":"A randomized trial of a transglutaminase 2 inhibitor for celiac disease","volume":"385","author":"D Schuppan","year":"2021","journal-title":"N Engl J Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T17:43:39Z","timestamp":1649267019000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266543"}},"subtitle":[],"editor":[{"given":"Lucienne","family":"Chatenoud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0266543","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]}}}