Poster Presentation International Celiac Disease Symposium 2026

IL-2 release in sera of children with treated CeD upon gluten challenge (#261)

Ilaria Mottola 1 , Roberta Mandile 1 , Roberta Esposito 2 3 , Antonia Amodio 3 , Lorenzo D'Antonio 1 , Mariantonia Maglio 1 , Valentina Discepolo 1 , Riccardo Troncone 1 , Carmen Gianfrani 3 , RENATA AURICCHIO 1
  1. Department of Translational Medical Science , European Laboratory for the Investigation of Food-Induced Diseases, Naples
  2. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Caserta, Italy
  3. Department of Bio-Medical Sciences, CNR, Institute of Biochemistry and Cell Biology, Naples

Background

Serum interleukin(IL)-2 release following short gluten challenge (SGC) is an early marker of gluten-specific T-cell activation in adults with treated celiac disease (CeD)[1]. However, serum IL-2 response in pediatric CeD is unexplored. We aimed to determine whether IL-2 is induced in blood of young subjects with treated CeD after gluten exposure.

Methods

Eleven patients with biopsy-proven CeD (mean age 10.6 years, range 5.7–20.8) underwent a standardized 3-day SGC (7g gluten/day). At baseline, all were asymptomatic, had negative celiac serology, and had maintained a GFD for at least 6 months (mean 4.29 years, range 1.1–19.0). Serum samples were collected at baseline (0h) and at 4h and 6h after the first gluten exposure. Serum IL-2 concentrations were measured by an ultrasensitive electrochemiluminescence immunoassay (S-PLEX, MesoScale Discovery). Gliadin-specific T-cell reactivity was assessed by IFN-γ-ELISPOT in peripheral blood mononuclear cells (SFC/10⁶PBMCs) at both baseline (Day0) and after 6 days (Day6).

Results

SGC induced a rapid IL-2 response and a robust gliadin-specific IFN-γ response in PBMCs. Serum IL-2 increased significantly at both 4h (563fg/ml range 70-1710; p=0.0049) and 6h (606fg/ml range 146-1516; p=0.001) compared to baseline (135fg/ml; range 54-308). Using a ≥2-fold increase, 72%(8/11) and 81%(9/11) of patients were classified as IL-2 responders at 4h and 6h, respectively, while 55% experienced mild gluten-related symptoms. Serum IL-2 strongly correlated with IFN-γ-ELISPOT responses. At Day6, gliadin-reactive T cells were detected in 67% of patients. Notably, DQ2.5-restricted dominant peptides eliciting stronger IFN-γ responses than gliadin (mean SFC/10⁶PBMCs: 54 for peptides vs. 23  for gliadin), compared to Day0 response (mean 32  for peptides vs. 9.7  for gliadin).

Conclusions

SGC induces an early IL-2 response in pediatric CeD. These findings extend observations from adults and identify serum IL-2 as a sensitive, minimally invasive biomarker of gluten-induced immune activation, supporting its use in pediatric diagnostic and therapeutic strategies.

  1. Goel G, Tye-Din JA, Qiao SWet al., Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Sci Adv. 2019. doi: 10.1126/sciadv.aaw7756