{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:48:43Z","timestamp":1791899323620,"version":"4.3.4"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the ITAMA project under the international cooperation program INTERREG V-A","award":["JS-Code C1-1.1-18"],"award-info":[{"award-number":["JS-Code C1-1.1-18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Coeliac disease (CD) is frequently underdiagnosed with a consequent heavy burden in terms of morbidity and health care costs. Diagnosis of CD is based on the evaluation of symptoms and anti-transglutaminase antibodies IgA (TGA-IgA) levels, with values above a tenfold increase being the basis of the biopsy-free diagnostic approach suggested by present guidelines. This study showcased the largest screening project for CD carried out to date in school children (n=20,000) aimed at assessing the diagnostic accuracy of minimally invasive finger prick point-of-care tests (POCT) which, combined with conventional celiac serology and the aid of an artificial intelligence-based system, may eliminate the need for intestinal biopsy. Moreover, this study delves deeper into the \u201ccoeliac iceberg\u201d in an attempt to identify people with disorders who may benefit from a gluten-free diet, even in the absence of gastrointestinal symptoms, abnormal serology and histology. This was achieved by looking for TGA-IgA mucosal deposits in duodenal biopsy. This large European multidisciplinary health project paves the way to an improved quality of life for patients by reducing the costs for diagnosis due to delayed findings of CD and to offer business opportunities in terms of diagnostic tools and support.<\/jats:p>","DOI":"10.3390\/pediatric14020037","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"293-311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Recognizing the Emergent and Submerged Iceberg of the Celiac Disease: ITAMA Project\u2014Global Strategy Protocol"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-4013","authenticated-orcid":false,"given":"Giuseppe","family":"Magazz\u00f9","sequence":"first","affiliation":[{"name":"Dipartimento di Patologia Umana dell\u2019Adulto e dell\u2019Et\u00e0 Evolutiva \u201cGaetano Barresi\u201d, Universit\u00e0 di Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Aquilina","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Mater Dei Hospital, 2090 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Barbara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mater Dei Hospital, 2090 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Bondin","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Mater Dei Hospital, 2090 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6243-7732","authenticated-orcid":false,"given":"Ignazio","family":"Brusca","sequence":"additional","affiliation":[{"name":"Ospedale Fatebenefratelli, Buccheri La Ferla, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Bugeja","sequence":"additional","affiliation":[{"name":"AcrossLimits Ltd., 4013 Birkirkara, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-4912","authenticated-orcid":false,"given":"Mark","family":"Camilleri","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mater Dei Hospital, 2090 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6522-1259","authenticated-orcid":false,"given":"Donato","family":"Cascio","sequence":"additional","affiliation":[{"name":"Dipartimento di Fisica e Chimica-\u201cE. 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Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"180","DOI":"10.14309\/ajg.0000000000000751","article-title":"Mass Screening for Celiac Disease: The Autoimmunity Screening for Kids Study","volume":"116","author":"Stahl","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1136\/bmj.39405.472975.80","article-title":"Population screening for coeliac disease in primary care by district nurses using a rapid antibody test: Diagnostic accuracy and feasibility study","volume":"335","author":"Szabados","year":"2007","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Costa, S., Astarita, L., Ben-Hariz, M., Curr\u00f2, G., Dolinsek, J., Kansu, A., Magazzu\u2019, G., Marvaso, S., Micetic-Turku, D., and Pellegrino, S. (2014). A Point-of-Care test for facing the burden of undiagnosed celiac disease in the Mediterranean area: A pragmatic design study. BMC Gastroenterol., 14.","DOI":"10.1186\/s12876-014-0219-5"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/MCG.0000000000001081","article-title":"Diagnostic Accuracy of Point of Care Tests for Diagnosing Celiac Disease: A Systematic Review and Meta-Analysis","volume":"53","author":"Singh","year":"2019","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e001152","DOI":"10.1136\/bmjpo-2021-001152","article-title":"Early diagnosis of coeliac disease in the Preventive Youth Health Care Centres in the Netherlands: Study protocol of a case finding study (GLUTENSCREEN)","volume":"5","author":"Akker","year":"2021","journal-title":"BMJ Paediatr. Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/apa.15514","article-title":"Point-of-Care test screening versus Case finding for paediatric coeliac disease: A pragmatic study in primary care","volume":"110","author":"Primavera","year":"2020","journal-title":"Acta Paediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/MCG.0000000000000962","article-title":"Diagnostic Yield of 2 Strategies for Adult Celiac Disease Identification in Primary Care","volume":"53","author":"Scoglio","year":"2019","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(94)90989-X","article-title":"Coeliac disease in the year 2000: Exploring the iceberg","volume":"343","author":"Catassi","year":"1994","journal-title":"Lancet"},{"key":"ref_17","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":"Halttunen","year":"2004","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0140-6736(96)90540-1","article-title":"Does cryptic gluten sensitivity play a part in neurological illness?","volume":"347","author":"Hadjivassiliou","year":"1996","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.2337\/db08-0962","article-title":"Majority of Children With Type 1 Diabetes Produce and Deposit Anti-Tissue Transglutaminase Antibodies in the Small Intestine","volume":"58","author":"Maglio","year":"2009","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Costa, S., Curr\u00f2, G., Pellegrino, S., Lucanto, M.C., Tuccari, G., Ieni, A., Visalli, G., Magazz\u00f9, G., and Santoro, D. (2018). Case report on pathogenetic link between gluten and IgA nephropathy. BMC Gastroenterol., 18.","DOI":"10.1186\/s12876-018-0792-0"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1212\/01.wnl.0000196480.55601.3a","article-title":"Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia","volume":"66","author":"Hadjivassiliou","year":"2006","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3389\/fphar.2020.00341","article-title":"Current Evidence on Computer-Aided Diagnosis of Celiac Disease: Systematic Review","volume":"11","author":"Molder","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.knosys.2017.03.006","article-title":"Designing rule-based fuzzy systems for classification in medicine","volume":"124","author":"Pota","year":"2017","journal-title":"Knowl.-Based Syst."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1038\/s41598-021-84951-x","article-title":"Precision medicine and machine learning towards the prediction of the outcome of potential celiac disease","volume":"11","author":"Piccialli","year":"2021","journal-title":"Sci Rep."},{"key":"ref_25","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":"ref_26","doi-asserted-by":"crossref","unstructured":"Singh, A.D., Ellias, S., Singh, P., Ahuja, V., and Makharia, G.K. (2021). The Prevalence of the Celiac Disease in Patients with Dyspepsia: A Systematic Review and Meta-Analysis. Am. J. Dig. Dis., 1\u201313.","DOI":"10.1007\/s10620-021-07142-8"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1365-2036.2006.02997.x","article-title":"Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease","volume":"24","author":"Salmi","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_28","first-page":"741","article-title":"Point of care testing for paediatric coeliac disease in the new ESPGHAN era","volume":"109","author":"Lau","year":"2017","journal-title":"Rev. Espa\u00f1ola Enferm. Dig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/j.cgh.2018.09.032","article-title":"Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study","volume":"17","author":"Tangermann","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/bmj.315.7107.540","article-title":"How to read a paper. Papers that report diagnostic or screening tests","volume":"315","author":"Greenhalgh","year":"1997","journal-title":"BMJ."},{"key":"ref_31","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. 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