Dupilumab opens a therapeutic window in food protein–induced enterocolitis syndrome by unlicensing dendritic cells

Background: Food-protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated reaction to food antigens for which no disease-modifying treatment exists. The mechanistic heterogeneity of FPIES-spanning multiple incompletely understood immune pathways-has hindered the prioritization of therapies in clinical trials. Objective: In this observational study, we sought to determine whether dupilumab, an mAB that is an IL-4 receptor-alpha antagonist, can induce clinical remission in FPIES. Methods: chemoattractant receptor-homologous molecule positive T-cell subsets before and after treatment; open food challenges assessed clinical tolerance. Results: All 7 additional patients (ages 2-58 years; triggers: milk, soy, rice, wheat, shellfish) achieved unrestricted dietary tolerance within 3 months, mirroring the immunophenotypic trajectory of the index case. All patients had provided consent under Western Institutional Review Board (protocol no. 20121950). Conclusions: Dupilumab rapidly and durably abrogated food reactivity across diverse FPIES phenotypes associated with downregulated dendritic-cell OX40L. These findings identify the IL-4/IL-13-OX40L axis as a tractable therapeutic target and support formal trials of dupilumab-including high-dose "rescue" regimens-in acute and chronic FPIES.