Diagnostic potential of allergen-specific lymphocyte stimulation test in hen's egg yolk-induced, food protein-induced enterocolitis syndrome.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy frequently triggered by hen's egg yolk (EY) in Japan. The lack of specific biomarkers hinders prompt diagnosis and appropriate management. Although oral food challenges are the diagnostic reference standard, their invasiveness and associated risks limit their feasibility in routine clinical practice. Objective: This study aimed to assess the diagnostic utility of the allergen-specific lymphocyte stimulation test (ALST) for EY-induced FPIES. Methods: We enrolled 71 infants diagnosed with EY-FPIES according to International Consensus Guidelines, along with 20 age-matched controls with allergic diseases other than FPIES. Peripheral blood mononuclear cells were stimulated with lipopolysaccharide-free EY and egg white (EW) extracts. The stimulation index (SI), representing antigen-specific lymphocyte responses, was calculated, and the EY/EW SI ratio was evaluated by receiver operating characteristic curve analysis. Results: Although EY-SI values were higher in the EY-FPIES group than in controls, the difference was not significant. In contrast, the EY-SI/EW-SI ratio showed modest diagnostic accuracy (area under curve = 0.68). At a cutoff of 1.75, sensitivity was 50.7%, specificity 80.0%, positive predictive value 90.0%, and negative predictive value 31.0%. Notably, EW-specific IgE correlated with the EY-SI/EW-SI ratio but not with EW-SI, suggesting that ALST was not due to simple cross-reactivity with EW. Conclusion: The EY/EW lymphocyte response ratio may serve as a supportive diagnostic biomarker for EY-FPIES. Despite its limited sensitivity, the high specificity and positive predictive value suggest that ALST could help reduce reliance on invasive oral food challenges in clinical practice.