Fecal-specific IgE as a Noninvasive and Complementary Biomarker for Mucosal Food Allergy: A Clinical Validation Study

Background : Conventional diagnostic tools for food allergy (FA), such as the skin prick test (SPT) and serum allergen-specific IgE (sIgE, formerly RAST), primarily detect systemic sensitization and may fail to capture localized mucosal immune responses. Measurement of fecal-specific IgE (f-sIgE) offers a noninvasive means to assess intestinal allergic inflammation. Objective : To validate f-sIgE as a complementary biomarker for mucosal FA and examine its diagnostic accuracy compared with standard systemic tests and oral food challenge (OFC). Methods : Forty-one children with clinically suspected FA confirmed by OFC underwent SPT, serum sIgE (kU/L), and f-sIgE (kU/g) testing for ten common allergens (milk, egg, peanut, hazelnut, wheat, soy, fish, tree nuts, shellfish, and apple). Fecal samples were processed using a pH-adjusted, protease-inhibited buffer and analyzed by immunoblotting. Diagnostic performance metrics (sensitivity, specificity, correlation with OFC) were calculated using a predefined f-sIgE cut-off of 3.5 kU/g. Results : Of 41 participants, 17 (41.5%) were positive for f-sIgE despite negative SPT results. Seven showed discordant allergen-specific patterns between serum and fecal IgE. One representative case exhibited markedly elevated fecal hazelnut IgE (>100 kU/g) with symptom resolution following maternal dietary elimination. f-sIgE correlated strongly with OFC outcomes (r = 0.91, p < 0.01), yielding 89% sensitivity and 92% specificity at the 3.5 kU/g threshold. Conclusions : f-sIgE reflects local IgE production distinct from systemic sensitization and complements conventional tests for FA. These findings suggest f-sIgE as a promising noninvasive biomarker of mucosal allergic sensitization and may inform future development of standardized fecal IgE assays after multicenter validation.