Enhancing the diagnostic accuracy of the IgE crosslinking-induced luciferase expression (EXiLE) method for walnut allergy

Background: Walnut (Juglans regia) frequently triggers nut allergies in the United Kingdom and in the United States, with increasing cases in Japan. While oral food challenges (OFCs) are the definitive method for diagnosing these allergies, they pose the risk of symptom provocation, necessitating safer alternative tests. Our aim here was to evaluate the diagnostic utility of IgE (immunoglobulin E) crosslinking-induced luciferase expression (EXiLE) for walnut allergy compared with the walnut-specific IgE (sIgE) test, Jug r 1-sIgE test, and skin prick test (SPT). Methods: This retrospective study analyzed 55 patients tested for walnut allergy (WA) at Fujita Health University Bantane Hospital from January 2021 to December 2023. Among them, 38 had allergic reactions to walnuts based on history or OFCs and 17 did not. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC) of the receiver operating characteristic curve. Results: The EXiLE method (AUC = 0.938) exhibited superior diagnostic accuracy compared to the walnut-sIgE and comparable performance to Jug r 1-sIgE and SPT. The optimal cutoff value of 1.26-fold change demonstrated high sensitivity (0.92), specificity (0.88), positive predictive value (0.92), and negative predictive value (0.82). The EXiLE method yielded positive results in all three cases with negative Jug r 1-sIgE (< 0.35 U^A/mL). Conclusion: The EXiLE method showed high sensitivity and specificity for diagnosing WA, indicating its potential clinical utility. Furthermore, the combination of Jug r 1-sIgE and EXiLE may enhance diagnostic accuracy. Future large-scale studies are warranted to confirm these findings and establish comprehensive diagnostic protocols.