{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:16:51Z","timestamp":1760188611284,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background &amp; Aims: Determining whether patients with lymphocytic enteritis (LE) have coeliac disease is a challenge. We analysed the variables associated with a low-grade coeliac enteropathy diagnosis in patients with suspected coeliac disease but without villous atrophy, and developed a scoring system to identify them. Methods: We collected data from 2010 through to 2016 on patients with lymphocytic enteritis and persistent symptoms compatible with the clinical spectrum of coeliac disease. One hundred and four patients starting on a gluten-free diet (GFD) were included. Duodenal biopsies were collected before the GFD and analysed for numbers of CD3+ T-cell receptor gamma delta+ (TCR\u03b3\u03b4+), and CD3\u2212 intraepithelial lymphocytes. We performed a logistic regression analysis to identify factors associated with a low-grade coeliac enteropathy diagnosis. Results: Sixty-two patients achieved clinical remission after the GFD. Fifty of these 62 patients were diagnosed with low-grade coeliac enteropathy. Multivariate analysis identified the presence of &gt;25% intraepithelial lymphocytosis, HLA-DQ2.5, positive serology, and increased numbers of TCR\u03b3\u03b4+ cells with a low-grade coeliac enteropathy diagnosis. We developed a scoring system that identified patients with an area under the ROC curve (AUC) of 0.91. Scores of &gt;10 had 86% sensitivity and 85% specificity. Conclusion: We developed a scoring system that identifies patients likely to be diagnosed with low-grade coeliac enteropathy with an AUC value of 0.91.<\/jats:p>","DOI":"10.3390\/nu11051050","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T03:57:07Z","timestamp":1557719827000},"page":"1050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Scoring System for Identifying Patients Likely to Be Diagnosed with Low-Grade Coeliac Enteropathy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1489-504X","authenticated-orcid":false,"given":"Fernando","family":"Fern\u00e1ndez-Ba\u00f1ares","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de enfermedades hep\u00e1ticas y digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de enfermedades hep\u00e1ticas y digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merc\u00e8","family":"Rosinach","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de enfermedades hep\u00e1ticas y digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4099-505X","authenticated-orcid":false,"given":"Beatriz","family":"Arau","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de enfermedades hep\u00e1ticas y digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5618-7984","authenticated-orcid":false,"given":"Roger","family":"Garc\u00eda-Puig","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarisa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Trist\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4023-8868","authenticated-orcid":false,"given":"Yamile","family":"Zabana","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de enfermedades hep\u00e1ticas y digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Esteve","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitari MutuaTerrassa, 08221 Terrassa, Barcelona, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de enfermedades hep\u00e1ticas y digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7110","DOI":"10.3748\/wjg.v21.i23.7110","article-title":"Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity","volume":"21","author":"Elli","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_2","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":"ref_3","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":"Koskinen","year":"2008","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1365-3083.1992.tb02881.x","article-title":"Phenotypical and functional characterization of small intestinal TCR \u03b3 \u03b4+ T cells incoeliac disease","volume":"35","author":"Rust","year":"1992","journal-title":"Scand. J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jpeds.2013.11.024","article-title":"Gluten sensitivity: Celiac lite versus celiac like","volume":"164","author":"Husby","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1053\/j.gastro.2012.01.020","article-title":"Irritable bowel syndrome and gluten sensitivity without celiac disease: Separating the wheat from the chaff","volume":"142","author":"Ferch","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1111\/nmo.12216","article-title":"Non-celiac gluten sensitivity: Clinical relevance and recommendations for future research","volume":"25","author":"Mooney","year":"2013","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Popp, A., and M\u00e4ki, M. (2019). Gluten-Induced Extra-Intestinal Manifestations in Potential Celiac Disease\u2014Celiac Trait. Nutrients, 11.","DOI":"10.3390\/nu11020320"},{"key":"ref_9","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":"ref_10","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1136\/gut.2006.095299","article-title":"Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: Clinical relevance of lymphocytic enteritis","volume":"55","author":"Esteve","year":"2006","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.dld.2012.03.006","article-title":"Lymphocytic duodenosis: Aetiology and long-term response to specific treatment","volume":"44","author":"Rosinach","year":"2012","journal-title":"Dig. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1111\/j.1365-2036.2010.04477.x","article-title":"A prospective study into the aetiology of lymphocytic duodenosis","volume":"32","author":"Aziz","year":"2010","journal-title":"Aliment Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rosinach, M., Fern\u00e1ndez-Ba\u00f1ares, F., Carrasco, A., Ibarra, M., Temi\u00f1o, R., Salas, A., and Esteve, M. (2016). Double-blind randomized clinical trial: Gluten versus placebo rechallenge in patients with lymphocytic enteritis and suspected celiac disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157879"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.12691\/ijcd-4-1-1","article-title":"Intraepithelial lymphocyte normal cut-off level in celiac disease: The debate continues","volume":"4","author":"Lerner","year":"2016","journal-title":"Int. J. Celiac Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1136\/gut.12.12.988","article-title":"Quantitation of intraepithelial lymphocytes in human jejunum","volume":"12","author":"Ferguson","year":"1971","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1136\/jcp.55.5.393","article-title":"Quantitation of intraepithelial lymphocytes in human duodenum: What is normal?","volume":"55","author":"Hayat","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1365-2036.2011.04578.x","article-title":"Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology","volume":"33","author":"Pellegrino","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/jcp.55.6.424","article-title":"Is a raised intraepithelial lymphocyte count with normal duodenal villus architecture clinically relevant?","volume":"55","author":"Mahadeva","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/0140-6736(92)91262-7","article-title":"Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic susceptibility to coeliac disease","volume":"339","author":"Holm","year":"1992","journal-title":"Lancet"},{"key":"ref_20","first-page":"285","article-title":"Intraepithelial lymphocytes and coeliac disease: Permanent changes in CD3\u2212\/CD7+ and T cell receptor \u03b3\u03b4 subsets studied by flow cytometry","volume":"89","author":"Camarero","year":"2000","journal-title":"Acta Paediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jim.2010.09.002","article-title":"Flow cytometry of intestinal intraepithelial lymphocytes in celiac disease","volume":"363","author":"Leon","year":"2011","journal-title":"J. Immunol. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Ba\u00f1ares, F., Carrasco, A., Garc\u00eda-Puig, R., Rosinach, M., Gonz\u00e1lez, C., Alsina, M., Loras, C., Salas, A., Viver, J.M., and Esteve, M. (2014). Intestinal intraepithelial lymphocyte cytometric pattern is more accurate than subepithelial deposits of anti-tissue transglutaminase IgA for the diagnosis of coeliac disease in lymphocytic enteritis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101249"},{"key":"ref_23","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":"ref_24","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":"Salmi","year":"2006","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.3748\/wjg.15.1331","article-title":"Impact of mass screening for gluten-sensitive enteropathy in working population","volume":"15","author":"Alsina","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1136\/gutjnl-2017-314853","article-title":"Outcome measures in coeliac disease trials: The Tampere recommendations","volume":"67","author":"Ludvigsson","year":"2018","journal-title":"Gut"},{"key":"ref_27","unstructured":"R Core Team (2018). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http:\/\/www.R-project.org\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/gutjnl-2011-301346","article-title":"The Oslo definitions for coeliac disease and related terms","volume":"62","author":"Ludvigsson","year":"2013","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1111\/j.1572-0241.1999.983_f.x","article-title":"Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: Disappointing in clinical practice","volume":"94","author":"Rostami","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/j.1365-2036.2008.03652.x","article-title":"Diagnostic value of duodenal antitissue transglutaminase antibodies in gluten-sensitive enteropathy","volume":"27","author":"Santaolalla","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sapone, A., Lammers, K.M., Casolaro, V., Cammarota, M., Giuliano, M.T., De Rosa, M., Stefanile, R., Mazzarella, G., Tolone, C., and Russo, M.I. (2011). Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: Celiac disease and gluten sensitivity. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-23"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1111\/j.1572-0241.2003.07456.x","article-title":"Intraepithelial lymphocytes in celiac disease","volume":"98","author":"Kaukinen","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1136\/gut.32.11.1412","article-title":"Increase in \u03b3\/\u03b4 T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease","volume":"32","author":"Holm","year":"1991","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Maglio, M., Ziberna, F., Aitoro, R., Discepolo, V., Lania, G., Bassi, V., Miele, E., Not, T., Troncone, R., and Auricchio, R. (2017). Intestinal production of anti-tissue transglutaminase 2 antibodies in patients with diagnosis other than celiac disease. Nutrients, 9.","DOI":"10.3390\/nu9101050"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/5\/1050\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:50:51Z","timestamp":1760187051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/5\/1050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,10]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["nu11051050"],"URL":"https:\/\/doi.org\/10.3390\/nu11051050","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2019,5,10]]}}}