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

TL;DR

This study finds that a specific gene variation in interleukin-15 is linked to a higher risk of celiac disease in children.

Contribution

The study identifies protective and risk-associated IL-15 gene variants in pediatric celiac disease patients.

Findings

The IL-15 SNP rs2857261 A/A genotype is more common in celiac disease patients than controls.

A/G and G/G IL-15 genotypes are protective against celiac disease.

Serum IL-15 levels are elevated in newly diagnosed celiac disease patients.

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.

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.

The online version contains supplementary material available at 10.1007/s00431-025-06108-6.

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