Serum nuclear alarmins associate with IgE-mediated food sensitization, but have no role in effector response to food challenge.

Abstract

Nuclear alarmins have emerged as promising biomarkers and potential therapeutic targets in the pathophysiology of food allergy (FA). In this context, the present study evaluated baseline and post-oral food challenge (OFC) levels of thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and the anti-inflammatory cytokine interleukin-10 (IL-10) in children with suspected IgE-mediated food allergy (IgE-FA). Thirty-five children with a suggestive history and proven IgE sensitization to food(s) and 20 healthy controls (HC) were enrolled. Serum samples were obtained before and after OFC and analyzed for TSLP, IL-25, and IL-10. Twenty-one children had a positive OFC (IgE-FA, Group-1) and 14 had a negative OFC (IgE-sensitized, Group-2). Baseline serum TSLP and IL-25 levels were significantly higher in both patient groups than in HC (p < 0.001, p = 0.004, p = 0.001, and p = 0.011, respectively). No significant post-challenge change was observed. Multivariate analysis identified younger age, atopic dermatitis, and IgE-sensitization as independent factors associated with higher TSLP levels. Serum TSLP and IL-25 are elevated in children with IgE-mediated food sensitization, irrespective of clinical reactivity. These findings suggest that epithelial alarmins play a key role in the induction of sensitization rather than in the effector response of FA, supporting their potential as early biomarkers of allergic predisposition. This study demonstrates that serum thymic stromal lymphopoietin (TSLP) and interleukin-25 (IL-25) are significantly elevated in children with IgE-mediated food sensitization, regardless of clinical reactivity. It provides novel human data showing that epithelial alarmins reflect the sensitization phase rather than the effector response of food allergy (FA). The study bridges experimental findings and clinical observations, offering translational insight into early immunologic events driving food sensitization. Younger age and the presence of atopic dermatitis were identified as independent predictors of higher serum TSLP levels. Recognition of alarmins as early immune mediators highlights their potential as preventive and therapeutic targets in pediatric FA.