{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:40:43Z","timestamp":1792662043118,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Part B Clinical"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The intraepithelial lymphogram, assessed by flow cytometry, has emerged as a valuable complementary tool for diagnosing celiac disease (CD). To optimize cutoff points for intraepithelial lymphocyte (IEL) subsets and to evaluate the diagnostic value of intraepithelial lymphogram in bulb and distal duodenal biopsies for active and potential CD in pediatric patients. This multicenter retrospective study included 190 pediatric patients (\u226414\u2009years old) who underwent duodenal biopsies for histological evaluation and flow cytometry. Patients were categorized as active CD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200954), potential CD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200969), and non\u2010CD controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200967). Total IELs, TcR\u03b3\u03b4 IELs, and sCD3\n                    <jats:sup>\u2212<\/jats:sup>\n                    IELs were quantified in bulb and distal duodenum biopsies. Cutoff points were optimized using ROC analysis. Agreement between cytometric patterns based on optimized and reference cutoffs was assessed using histological and serological criteria (Kappa coefficient). Sensitivity, specificity, and predictive values were evaluated for both biopsy sites. Active CD patients showed significantly increased total IELs and TcR\u03b3\u03b4 IELs, and decreased sCD3\n                    <jats:sup>\u2212<\/jats:sup>\n                    IELs in both anatomical regions. Optimized cutoff points for active CD were TcR\u03b3\u03b4 IELs &gt;11.1% in the bulb and in the distal duodenum, sCD3\n                    <jats:sup>\u2212<\/jats:sup>\n                    IELs &lt;6.4% in the bulb, and &lt;8.5% in the distal duodenum. These cutoffs demonstrated stronger concordance with serological and histological findings than the reference values. Sensitivity improved when both anatomical regions were analyzed. In the potential CD group, a significant decrease in sCD3\n                    <jats:sup>\u2212<\/jats:sup>\n                    IELs was observed only in the bulb, where more patients exhibited a complete celiac lymphogram. Optimizing IEL subsets cutoff points and the inclusion of bulb biopsies enhances the diagnostic performance of intraepithelial lymphograms for active and potential CD in pediatric patients.\n                  <\/jats:p>","DOI":"10.1002\/cyto.b.70084","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:02:37Z","timestamp":1792659757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing intraepithelial lymphogram for celiac disease diagnosis in children: Cut\u2010off points and the role of bulb biopsies"],"prefix":"10.1002","author":[{"given":"Laura Escart\u00edn","family":"Madurga","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition Hospital Cl\u00ednico Universitario Lozano Blesa  Zaragoza Spain"},{"name":"Department of Pediatrics University of Zaragoza  Zaragoza Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IISArag\u00f3n)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Jordan","family":"Mena","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition Hospital Cl\u00ednico Universitario Lozano Blesa  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4659-7378","authenticated-orcid":false,"given":"Carlos Nagore","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IISArag\u00f3n)  Zaragoza Spain"},{"name":"Department of Pediatrics Hospital Cl\u00ednico Universitario Lozano Blesa  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio Ros","family":"Arnal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan L\u00f3pez","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Immunology Hospital Cl\u00ednico Universitario Lozano Blesa  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Garc\u00eda","family":"Romero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IISArag\u00f3n)  Zaragoza Spain"},{"name":"Department of Pediatric Gastroenterology and Nutrition Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza Castej\u00f3n","family":"Ponce","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-9912","authenticated-orcid":false,"given":"Gerardo Rodr\u00edguez","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Zaragoza  Zaragoza Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IISArag\u00f3n)  Zaragoza Spain"},{"name":"Department of Pediatrics Hospital Cl\u00ednico Universitario Lozano Blesa  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"5","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1177\/2050640619844125","article-title":"European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten\u2010related disorders","volume":"7","author":"Al\u2010Toma A.","year":"2019","journal-title":"United European 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F.","year":"2019","journal-title":"Nutrients"},{"issue":"8","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","DOI":"10.3390\/nu16081117","article-title":"Intraepithelial lymphogram in the diagnosis of celiac disease in adult patients: A validation cohort","volume":"16","author":"Garc\u00eda\u2010Hoz C.","year":"2024","journal-title":"Nutrients"},{"issue":"2","key":"e_1_2_8_15_1","first-page":"25","article-title":"Citometr\u00eda de flujo en el diagn\u00f3stico de la enfermedad cel\u00edaca: linfograma intestinal","volume":"39","author":"Garc\u00eda\u2010Hoz C.","year":"2016","journal-title":"Gastroenterologia y Hepatologia"},{"issue":"1","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12865-018-0275-7","article-title":"Small\u2010intestinal TG2\u2010specific plasma cells at different stages of coeliac disease","volume":"19","author":"Hietikko M.","year":"2018","journal-title":"BMC 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T.","year":"2010","journal-title":"Digestive and Liver Disease"},{"issue":"1","key":"e_1_2_8_32_1","doi-asserted-by":"crossref","DOI":"10.1007\/s13317-016-0085-y","article-title":"Intraepithelial lymphocytes subsets in different forms of celiac disease","volume":"7","author":"S\u00e1nchez\u2010Casta\u00f1on M.","year":"2016","journal-title":"Auto Immunity Highlights"},{"issue":"1","key":"e_1_2_8_33_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/ajg.2015.387","article-title":"A prospective study on the usefulness of duodenal bulb biopsies in celiac disease diagnosis in children: Urging caution","volume":"111","author":"Taavela J.","year":"2016","journal-title":"American Journal of Gastroenterology"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/8974751","article-title":"The challenge of treatment in potential celiac disease","volume":"2019","author":"Trovato C. M.","year":"2019","journal-title":"Gastroenterology Research and Practice"},{"issue":"6","key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1177\/2050640616682181","article-title":"Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases","volume":"5","author":"Valle J.","year":"2017","journal-title":"United European Gastroenterology Journal"}],"container-title":["Cytometry Part B: Clinical Cytometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.b.70084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cyto.b.70084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.b.70084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:02:41Z","timestamp":1792659761000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cyto.b.70084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":34,"alternative-id":["10.1002\/cyto.b.70084"],"URL":"https:\/\/doi.org\/10.1002\/cyto.b.70084","archive":["Portico"],"relation":{},"ISSN":["1552-4949","1552-4957"],"issn-type":[{"value":"1552-4949","type":"print"},{"value":"1552-4957","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"2026-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cyto.b.70084"}}