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This case\u2013control and prospective cohort study included 54 newly diagnosed pediatric CD patients attending the Gastroenterology Clinic at Alexandria University Children\u2019s Hospital and 44 age- and sex-matched healthy controls. Demographics, clinical data, laboratory tests, Marsh classification, and IL-15 SNP (rs2857261) genotypes were analyzed. Follow-up after 9\u00a0months on a gluten-free diet (GFD) was conducted. The mean age of patients and controls was 8.62\u2009\u00b1\u20094.4 and 8.07\u2009\u00b1\u20094.7\u00a0years, respectively, with no significant difference (<jats:italic>p<\/jats:italic>\u2009=\u20090.55). Male representation was 48.1% in patients and 47.7% in controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.97). The most common presenting symptoms in CD patients were abdominal distension (61.11%) and failure to thrive (59.26%). Laboratory findings showed that mean anti-tissue transglutaminase immunoglobulin A was 103\u2009\u00b1\u2009168 U\/ml, and anti-endomysium immunoglobulin A was positive in 51.85% of patients. Histopathological assessment revealed Marsh 3C as the most common finding (37%), while 37% of patients were diagnosed without biopsy. IL-15 SNP (rs2857261) analysis showed a significantly higher prevalence of the A\/A genotype in CD patients compared to controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The A\/G and G\/G genotypes were protective against CD, with odds ratios of 0.088 and 0.079, respectively. No significant associations were observed between IL-15 genotypes and clinical, laboratory, or histological variables. After 6 to 9\u00a0months on a GFD, genotype did not significantly influence symptom resolution (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05).<\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>: Serum IL-15 levels are elevated in newly diagnosed pediatric CD patients. The IL-15 SNP (rs2857261) A\/A genotype is associated with increased susceptibility to CD, while the A\/G and G\/G genotypes appear protective. These findings highlight IL-15 as a potential biomarker and therapeutic target in CD. Further large-scale studies are warranted to validate these findings and explore therapeutic applications.<jats:table-wrap>\n              <jats:table>\n                <jats:tbody>\n                  <jats:tr>\n                    <jats:td align=\"left\">\n                      <jats:bold>What is Known:<\/jats:bold>\u2022 <jats:italic>Celiac disease is an immune-mediated enteropathy linked to HLA-DQ2\/DQ8 alleles, with IL-15 playing a key role in its pathogenesis.<\/jats:italic>\u2022 <jats:italic>Variability in IL-15 genetic polymorphisms has been suggested but remains underexplored in pediatric populations.<\/jats:italic>\n                    <\/jats:td>\n                  <\/jats:tr>\n                  <jats:tr>\n                    <jats:td align=\"left\">\n                      <jats:bold>What is New:<\/jats:bold>\u2022 <jats:italic>This study identifies the IL-15 SNP (rs2857261) A\/A genotype as a risk factor for CD, while A\/G and G\/G genotypes are protective.<\/jats:italic>\u2022 <jats:italic>Elevated serum IL-15 levels in newly diagnosed patients highlight its potential as a biomarker and therapeutic target.<\/jats:italic>\n                    <\/jats:td>\n                  <\/jats:tr>\n                <\/jats:tbody>\n              <\/jats:table>\n            <\/jats:table-wrap>\n          <\/jats:p>","DOI":"10.1007\/s00431-025-06108-6","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:19:04Z","timestamp":1745389144000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-15 gene polymorphism in children with celiac disease: a single-center experience"],"prefix":"10.1007","volume":"184","author":[{"given":"Mohamed Abdelfadeel","family":"Ragab","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-8893","authenticated-orcid":false,"given":"Omneya M.","family":"Omar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omneya","family":"Badreldin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahed","family":"Baddour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hend A.","family":"Yassin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada M.","family":"Zeitoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"issue":"4","key":"6108_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.5409\/wjcp.v10.i4.53","volume":"10","author":"Y Sahin","year":"2021","unstructured":"Sahin Y (2021) Celiac disease in children: a review of the literature. 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Ethical approval for the study was obtained from the local Faculty of Medicine Ethics Committee. (IRB code 00012098\u2011FWA: No. 00018699. Ethics approval number: No. 0201709).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors thank the staff members of Pediatric Gastroenterology and Nutrition and for their collaboration during the data collection","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"308"}}