{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:04:32Z","timestamp":1760151872999,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: The diagnosis of celiac disease (CD) has been substantially improved with the availability of highly sensitive CD-specific IgA-TG2, Ig-GDP, and IgA-EMA. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published (2012) and updated (2020) diagnostic criteria for CD in order to simplify CD diagnosis and to avoid biopsies in selected patients. Methods: A prospective study including 5641 pediatric patients (0\u201316 years old) from January 2012 to January 2019 was performed. CD diagnosis was made according to the ESPGHAN algorithm. The objective of this study was to evaluate the utility of biomarkers and the relationship between TGA-IgA and EMA titers. Results: CD diagnoses were confirmed in 113 patients, 110 were IgA-TG2-positive and 3 (2.7%) had IgA deficiency. The diagnosis was made by serologic tests in 95 (84.1%) patients. Only 18 (15.9%) patients underwent intestinal biopsy. We obtained 100% concordance between IgA-EMA and positive results for IgA-TG2 \u2265 10 ULN with IgA-EMA antibody titer \u2265 1:80. Conclusions: This study provides evidence of a positive correlation between IgA-TG2 antibody serum levels and IgA-EMA. The diagnosis could be guaranteed with strict application of IgA-TG2 values \u2265 10 ULN (confirmed by subsequent testing) plus the serological response to the gluten-free diet (GFD).<\/jats:p>","DOI":"10.3390\/ijerph19095020","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"5020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Celiac Disease by Minimally Invasive Biomarkers in a Spanish Pediatric Population"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6329-7409","authenticated-orcid":false,"given":"Julia Mar\u00eda","family":"Cabo del Riego","sequence":"first","affiliation":[{"name":"Clinical Analysis Laboratory, Department of Inmunology, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"},{"name":"Doctoral Programme in Medicine Clinical Research, International PhD School of the University of Santiago de Compostela (EDIUS), 15782 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jes\u00fas","family":"N\u00fa\u00f1ez Iglesias","sequence":"additional","affiliation":[{"name":"Department of Psiquiatry, Radiology, Public Health, Nursing and Medicine, University of Santiago de Compostela, 15705 A Coru\u00f1a, Spain"},{"name":"SNL Laboratory, School of Medicine and Dentistry, 15782 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Garc\u00eda-Plata Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Pediatric Gastrohepathology Unit of Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Paz Carreira","sequence":"additional","affiliation":[{"name":"Pediatric Gastrohepathology Unit of Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"\u00c1lvarez Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Department of Inmunology, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Dorado D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Statistical Health Counselling, Junta de Castilla y Le\u00f3n, 47001 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noa","family":"Villar Mallo","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Department of Inmunology, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Penedo Pita","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Department of Inmunology, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6169-8356","authenticated-orcid":false,"given":"Silvia","family":"Nov\u00edo Mall\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Psiquiatry, Radiology, Public Health, Nursing and Medicine, University of Santiago de Compostela, 15705 A Coru\u00f1a, Spain"},{"name":"SNL Laboratory, School of Medicine and Dentistry, 15782 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lola","family":"M\u00e1iz Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Department of Inmunology, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Freire-Garabal N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"SNL Laboratory, School of Medicine and Dentistry, 15782 A Coru\u00f1a, Spain"},{"name":"Department of Pharmacology, University of Santiago de Compostela, 15705 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Caio, G., Volta, U., Sapone, A., Leffler, D.A., De Giorgio, R., Catassi, C., and Fasano, A. (2019). Celiac disease: A comprehensive current review. BMC Med., 17.","key":"ref_1","DOI":"10.1186\/s12916-019-1380-z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0054-z","article-title":"Coeliac disease","volume":"5","author":"Lindfors","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.jaci.2015.01.044","article-title":"Celiac disease","volume":"135","author":"Green","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1053\/j.gastro.2017.06.002","article-title":"Accuracy in diagnosis of celiac disease without biopsies in clinical practice","volume":"153","author":"Werkstetter","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/pch\/18.5.246","article-title":"Antitissue transglutaminase antibody determination versus upper endoscopic bi-opsy diagnosis of paediatric celiac disease","volume":"18","author":"Saginur","year":"2013","journal-title":"Paediatr. Child Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1097\/MPG.0b013e3181677d6e","article-title":"Duodenal bulb biopsies in celiac disease: A multicenter study","volume":"47","author":"Bonamico","year":"2008","journal-title":"J. Pediatr. Gas-troenterol. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/MPG.0b013e3181a81384","article-title":"Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA\/IgG serum antibodies to tissue transglutaminase","volume":"50","author":"Dahlbom","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/MPG.0b013e3181ef8e50","article-title":"A biopsy is not always necessary to diagnose celiac disease","volume":"52","author":"Mubarak","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/MPG.0b013e3182470249","article-title":"Cor-relation 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":"ref_10","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/MPG.0b013e31821a23d0","article-title":"European Society for Pediatric Gastroenterology, Hepatology, and Nutri-tion Guidelines for the Diagnosis of Coeliac Disease","volume":"54","author":"Husby","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/MPG.0000000000002497","article-title":"European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020","volume":"70","author":"Husby","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13052-017-0392-6","article-title":"Coeliac disease in infants: Antibodies to deaminated gliadin peptide come first!","volume":"43","author":"Arigliani","year":"2017","journal-title":"Ital. J. Pediatr."},{"unstructured":"Kleinman, K., McDaniel, L., and Molloy, M. (2021). Manual Harriet Lane de pediatr\u00eda. The Johns Hopkins Hospital, Elsevier. [22nd ed.].","key":"ref_13"},{"key":"ref_14","first-page":"337","article-title":"Prevalencia de la enfermedad celiaca en donantes de sangre de la Comunidad de Madrid","volume":"99","author":"Garfia","year":"2007","journal-title":"Rev. Esp. Enferm. Dig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/00042737-199910000-00019","article-title":"The histopathology of coeliac disease: Time for a standardized report scheme for pathologists","volume":"11","author":"Oberhuber","year":"1999","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/archdischild-2013-303996","article-title":"Joint BSPGHAN and Coelic UK guidelines for the diagnosis and management of coeliac disease in children","volume":"98","author":"Murch","year":"2013","journal-title":"Arch. Dis. Child."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1001\/jama.2010.549","article-title":"Diagnostic testing for celiac disease among patients with abdominal symp-toms: A systematic review","volume":"303","author":"Jellema","year":"2010","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1038\/ajg.2012.219","article-title":"The Prevalence of celiac disease in the United States American","volume":"107","author":"Ludvigsson","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/ajg.2015.87","article-title":"Evaluation of the ESPGHAN celiac guidelines in a North American pediatric population","volume":"110","author":"Gidrewicz","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1136\/gutjnl-2017-314853","article-title":"Outcome measures in coeliac disease trials: The Tampere recom-mendations","volume":"67","author":"Ludvigsson","year":"2018","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1053\/j.gastro.2015.01.044","article-title":"Advances in diagnosis and management of celiac disease","volume":"148","author":"Kelly","year":"2015","journal-title":"Gastroenterology"},{"unstructured":"Grupo de Trabajo del Protocolo para el Diagn\u00f3stico Precoz de la Enfermedad Celiaca (2018). Protocolo para el Diagn\u00f3stico Precoz de la Enfermedad Celiaca.","key":"ref_22"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"630463","DOI":"10.1155\/2013\/630463","article-title":"Anti-actin IgA antibodies identify celiac disease patients with a Marsh 3 intestinal damage among subjects with moderate anti-TG2 levels","volume":"2013","author":"Schirru","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/MPG.0b013e318279887b","article-title":"Celiac dis-ease: The new proposed ESPGHAN diagnostic criteria do work well in a selected population","volume":"56","author":"Klapp","year":"2013","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"doi-asserted-by":"crossref","unstructured":"Ucci, F., Astarita, L., Abkari, A., Abu-Zekry, M., Attard, T., Ben Hariz, M., Bilbao, J.R., Boudraa, G., Boukthir, S., and Costa, S. (2014). Celiac Disease in the Mediterranean Area. BMC Gastroenterol., 14.","key":"ref_25","DOI":"10.1186\/1471-230X-14-24"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/MPG.0000000000000870","article-title":"ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study","volume":"62","author":"Donat","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1136\/bmj.39133.668681.BE","article-title":"Preendoscopy serological testing for coeliac disease: Evaluation of a clinical decision tool","volume":"334","author":"Hopper","year":"2007","journal-title":"BMJ"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.3748\/wjg.v16.i25.3144","article-title":"Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable?","volume":"16","author":"Sugai","year":"2010","journal-title":"World J. Gastroenterol."},{"doi-asserted-by":"crossref","unstructured":"Smarrazzo, A., Misak, Z., Costa, S., Mi\u010deti\u0107-Turk, D., Abu-Zekry, M., Kansu, A., Abkari, A., Bouziane-Nedjadi, K., Ben Hariz, M., and Roma, E. (2017). Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: A real life prospective study. BMC Gastroenterol., 17.","key":"ref_29","DOI":"10.1186\/s12876-017-0577-x"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1053\/j.gastro.2017.04.023","article-title":"Validation of antibody-based strategies for diagnosis of pediatric celiac disease without biopsy","volume":"153","author":"Wolf","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1515\/cclm-2013-1099","article-title":"Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease","volume":"53","author":"Oyaert","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/j.1651-2227.2010.02124.x","article-title":"Clinical accuracy of anti-tissue transglutaminase as screening test for celiac disease under 2 years","volume":"100","author":"Panetta","year":"2011","journal-title":"Acta Paediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/MPG.0b013e318216f2e5","article-title":"ESPGHAN Working Group on Coeliac Disease Diagnosis. Accuracy of diagnostic antibody tests for coeliac disease in children: Summary of an evidence report","volume":"54","author":"Giersiepen","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1053\/j.gastro.2018.12.010","article-title":"AGA Clinical practice update on diagnosis and monitoring of celiac disease: Changing utility of serology and histologic measures: Expert review","volume":"156","author":"Husby","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ejim.2018.11.012","article-title":"Management of celiac disease in daily clinical","volume":"61","author":"Elli","year":"2019","journal-title":"Eur. J. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4399","DOI":"10.3748\/wjg.v18.i32.4399","article-title":"Tissue transglutaminase levels above 100U\/mL and celiac disease: A prospective study","volume":"18","author":"Mubarak","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/MPG.0b013e31820a724d","article-title":"HLA-DQ genotyping combined with serological markers for the di-agnosis of celiac disease: Is intestinal biopsy still mandatory?","volume":"52","author":"Rebouissoux","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/9\/5020\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:42Z","timestamp":1760137062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/9\/5020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijerph19095020"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19095020","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}