{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:19:50Z","timestamp":1780327190285,"version":"3.54.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,7,24]],"date-time":"2014-07-24T00:00:00Z","timestamp":1406160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,24]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>It has always been known that anti-tissue transglutaminase 2 (anti-TG2) antibodies are produced in the small intestine. Their serum titres correlate with mucosal damage degree and decrease on a gluten-free diet (GFD).<\/jats:p>\n               <jats:p>We aimed to correlate intestinal anti-TG2 antibodies levels with degree of mucosal damage and GFD duration.<\/jats:p>\n               <jats:p>Thirty-four active, 71 potential and 24 CD patients on GFD for at least 2 years were enrolled. Anti-TG2 deposits were detected in intestinal biopsies by double immunofluorescence. Biopsies were cultured for 24 h with medium, and with gliadin peptic tryptic digest (PTG) or A-gliadin peptide 31\u201343 (P31-43). Anti-TG2 antibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay (ELISA). All active CD patients secreted high titres of anti-TG2 antibodies into culture medium that increased with the worsening of mucosal injury (Spearman's r = 0\u00b771; P &amp;lt; 0\u00b70001). Seventy of 71 potential CD patients and 15 of 24 treated CD patients secreted low titres of anti-TG2 antibodies into supernatants, eight of nine negative treated patients being on GFD for more than 10 years. An inverse correlation between antibody titres and duration of GFD was found, (Spearman's r = \u22120\u00b752; P &amp;lt; 0\u00b701). All active, 53 of 71 potential and six of 24 treated, CD patients showed anti-TG2 mucosal deposits. Five of six positive treated CD patients had been on GFD for fewer than 6 years and were also positive for secreted anti-TG2. In treated patients, PTG\/P31-43 was not able to induce secretion of anti-TG2 antibodies into culture medium.<\/jats:p>\n               <jats:p>Measurement of anti-TG2 antibodies in biopsy supernatants proved to be more sensitive than detection by immunofluorescence to reveal their intestinal production. Intestinal antiTG2 antibodies titres correlated positively with the degree of mucosal damage and inversely with the duration of GFD.<\/jats:p>","DOI":"10.1111\/cei.12366","type":"journal-article","created":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T11:07:44Z","timestamp":1398683264000},"page":"611-617","source":"Crossref","is-referenced-by-count":15,"title":["Intestinal titres of anti-tissue transglutaminase 2 antibodies correlate positively with mucosal damage degree and inversely with gluten-free diet duration in coeliac disease"],"prefix":"10.1093","volume":"177","author":[{"given":"A","family":"Tosco","sequence":"first","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Auricchio","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"},{"name":"European Laboratory for the Investigation of Food Induced Diseases (ELFID), University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Aitoro","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Ponticelli","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Primario","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Miele","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Rotondi Aufiero","sequence":"additional","affiliation":[{"name":"Institute of Food Sciences, Immunobiology, National Council Research, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Discepolo","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"},{"name":"European Laboratory for the Investigation of Food Induced Diseases (ELFID), University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Medical Translational Sciences, Section of Pediatrics, University Federico II, Naples, Italy"},{"name":"European Laboratory for the Investigation of Food Induced Diseases (ELFID), University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Maglio","sequence":"additional","affiliation":[{"name":"European Laboratory for the Investigation of Food Induced Diseases (ELFID), University Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,7,24]]},"reference":[{"key":"2021122010043865700_cei12366-bib-0001","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nri885","article-title":"Coeliac disease: dissecting a complex inflammatory disorder","volume":"2","author":"Sollid","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"2021122010043865700_cei12366-bib-0002","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nm0797-797","article-title":"Identification of tissue transglutaminase as the autoantigen of celiac disease","volume":"3","author":"Dieterich","year":"1997","journal-title":"Nat Med"},{"key":"2021122010043865700_cei12366-bib-0003","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1824-7288-36-25","article-title":"IgA anti-actin antibodies in children with celiac disease: comparison of immunofluorescence with ELISA assay in predicting severe intestinal damage","volume":"36","author":"Bazzigaluppi","year":"2010","journal-title":"Ital J Pediatr"},{"key":"2021122010043865700_cei12366-bib-0004","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/MPG.0b013e3182470249","article-title":"Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease","volume":"55","author":"Alessio","year":"2012","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2021122010043865700_cei12366-bib-0005","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/MPG.0b013e31821a23d0","article-title":"European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Guidelines for the diagnosis of coeliac disease","volume":"54","author":"Husby","year":"2012","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2021122010043865700_cei12366-bib-0006","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1542\/peds.2010-3762","article-title":"Specific celiac disease antibodies in children on a gluten-free diet","volume":"128","author":"Hogen Esch","year":"2011","journal-title":"Pediatrics"},{"key":"2021122010043865700_cei12366-bib-0007","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":"Korponay-Szabo","year":"2004","journal-title":"Gut"},{"key":"2021122010043865700_cei12366-bib-0008","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1572-0241.2002.05426.x","article-title":"Antiendomysial antibody detection in fecal supernatants: in vivo proof that small bowel mucosa is the site of antiendomysial antibody production","volume":"97","author":"Picarelli","year":"2002","journal-title":"Am J Gastroenterol"},{"key":"2021122010043865700_cei12366-bib-0009","first-page":"394","article-title":"Anti-reticulin antibody in jejunal juice in coeliac disease","volume":"21","author":"Mawhinney","year":"1975","journal-title":"Clin Exp Immunol"},{"key":"2021122010043865700_cei12366-bib-0010","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1080\/00365520510024151","article-title":"Usefulness of the organ culture system in the in vitro diagnosis of coeliac disease: a multicentre study","volume":"41","author":"Picarelli","year":"2006","journal-title":"Scand J Gastroenterol"},{"key":"2021122010043865700_cei12366-bib-0011","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1373\/clinchem.2005.061366","article-title":"Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis","volume":"52","author":"Carroccio","year":"2006","journal-title":"Clin Chem"},{"key":"2021122010043865700_cei12366-bib-0012","first-page":"85","article-title":"Organ culture system as a means to detect celiac disease","volume":"40","author":"Picarelli","year":"2010","journal-title":"Ann Clin Lab Sci"},{"key":"2021122010043865700_cei12366-bib-0013","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nm.2656","article-title":"High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions","volume":"18","author":"Di Niro","year":"2012","journal-title":"Nat Med"},{"key":"2021122010043865700_cei12366-bib-0014","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.4049\/jimmunol.166.6.4170","article-title":"Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease","volume":"166","author":"Marzari","year":"2001","journal-title":"J Immunol"},{"key":"2021122010043865700_cei12366-bib-0015","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1136\/bmj.38688.654028.AE","article-title":"Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children: validation study","volume":"332","author":"Kappler","year":"2006","journal-title":"BMJ"},{"key":"2021122010043865700_cei12366-bib-0016","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":"Tosco","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"2021122010043865700_cei12366-bib-0017","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.trsl.2012.10.010","article-title":"Usefulness of the organ culture system when villous height\/crypt depth ratio, intraepithelial lymphocyte count, or serum antibody tests are not diagnostic for celiac disease","volume":"161","author":"Picarelli","year":"2013","journal-title":"Transl Res"},{"key":"2021122010043865700_cei12366-bib-0018","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0140-6736(96)03060-7","article-title":"Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease","volume":"348","author":"Picarelli","year":"1996","journal-title":"Lancet"},{"key":"2021122010043865700_cei12366-bib-0019","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2172-9-6","article-title":"Secretion of celiac disease antibodies after in vitro gladin challenge is dependent on small-bowel mucosal transglutaminase2-specific IgA deposits","volume":"9","author":"Stenman","year":"2008","journal-title":"BMC Immunol"},{"key":"2021122010043865700_cei12366-bib-0020","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/00004836-200311000-00007","article-title":"Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease","volume":"37","author":"Tursi","year":"2003","journal-title":"J Clin Gastroenterol"},{"key":"2021122010043865700_cei12366-bib-0021","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/00042737-199910000-00019","article-title":"The histopathology of celiac disease: time for a standardized report scheme for pathologists","volume":"11","author":"Oberhuber","year":"1999","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"2021122010043865700_cei12366-bib-0022","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1053\/j.gastro.2008.11.040","article-title":"Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study","volume":"136","author":"Kurppa","year":"2009","journal-title":"Gastroenterology"},{"key":"2021122010043865700_cei12366-bib-0023","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1136\/gut.52.1.57","article-title":"An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients","volume":"52","author":"Mazzarella","year":"2003","journal-title":"Gut"},{"key":"2021122010043865700_cei12366-bib-0024","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/MPG.0b013e3181677067","article-title":"Immunoglobulin A anti-tissue transglutaminase antibody deposits in the small intestinal mucosa of children with no villous atrophy","volume":"47","author":"Tosco","year":"2008","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2021122010043865700_cei12366-bib-0025","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1111\/j.1572-0241.2005.41134.x","article-title":"Clinical, HLA and small bowel immunohistochemical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa","volume":"100","author":"Paparo","year":"2005","journal-title":"Am J Gastroenterol"},{"key":"2021122010043865700_cei12366-bib-0026","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/MCG.0b013e31802e70b1","article-title":"Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease","volume":"42","author":"Donaldson","year":"2008","journal-title":"J Clin Gastroenterol"},{"key":"2021122010043865700_cei12366-bib-0027","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4103\/0377-4929.81593","article-title":"Comparative study of histopathological Marsh grading with clinical and serological parameters in celiac iceberg of north India","volume":"54","author":"Kalhan","year":"2011","journal-title":"Indian J Pathol Microbiol"},{"key":"2021122010043865700_cei12366-bib-0028","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1053\/gast.1996.v110.pm8613040","article-title":"Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients","volume":"110","author":"Maiuri","year":"1996","journal-title":"Gastroenterology"},{"key":"2021122010043865700_cei12366-bib-0029","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/adc.2003.029603","article-title":"Mass screening for coeliac disease using antihuman transglutaminase antibody assay","volume":"89","author":"Tommasini","year":"2004","journal-title":"Arch Dis Child"},{"key":"2021122010043865700_cei12366-bib-0030","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1572-0241.2003.07284.x","article-title":"Reliability of antitransglutaminase antibodies as predictors of gluten-free diet compliance in adult celiac disease","volume":"98","author":"Vahedi","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"2021122010043865700_cei12366-bib-0031","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1097\/00042737-200106000-00008","article-title":"The serum IgA class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease. Results of an international multi-centre study. International Working Group on Eu-tTG","volume":"13","author":"Fabiani","year":"2001","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"2021122010043865700_cei12366-bib-0032","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3389\/fimmu.2012.00313","article-title":"The intestinal B-cell response in celiac disease","volume":"3","author":"Mesin","year":"2012","journal-title":"Front Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12366","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/177\/3\/611\/41789693\/cei12366.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/177\/3\/611\/41789693\/cei12366.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T16:26:26Z","timestamp":1641054386000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/177\/3\/611\/6421179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,24]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,7,24]]},"published-print":{"date-parts":[[2014,7,24]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12366","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,9]]},"published":{"date-parts":[[2014,7,24]]}}}