Interleukin-15 gene polymorphism in children with celiac disease: a single-center experience

乳糜泻患儿白细胞介素-15基因多态性:单中心经验

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Abstract

The purpose of this study is to evaluate the demographics, clinical presentation, laboratory findings, and gastrointestinal endoscopic findings in children with CD and assess their relationship with interleukin-15 (IL-15) single-nucleotide polymorphism (SNP) (rs2857261) and serum IL-15 levels. This case-control and prospective cohort study included 54 newly diagnosed pediatric CD patients attending the Gastroenterology Clinic at Alexandria University Children's 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 months on a gluten-free diet (GFD) was conducted. The mean age of patients and controls was 8.62 ± 4.4 and 8.07 ± 4.7 years, respectively, with no significant difference (p = 0.55). Male representation was 48.1% in patients and 47.7% in controls (p = 0.97). 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 ± 168 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 (p < 0.0001). 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 months on a GFD, genotype did not significantly influence symptom resolution (p > 0.05). CONCLUSIONS: 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. WHAT IS KNOWN: • Celiac disease is an immune-mediated enteropathy linked to HLA-DQ2/DQ8 alleles, with IL-15 playing a key role in its pathogenesis. • Variability in IL-15 genetic polymorphisms has been suggested but remains underexplored in pediatric populations. WHAT IS NEW: • 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. • Elevated serum IL-15 levels in newly diagnosed patients highlight its potential as a biomarker and therapeutic target.

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