Highly Accurate and Reproducible Diagnosis of Peanut Allergy Using Epitope Mapping

Abstract Background: Misdiagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood-based test using a Bead-Based Epitope Assay (peanut BBEA) has been developed on the LEAP cohort and then independently validated on the CoFAR2 and POISED cohorts. Methods: Development of the peanut BBEA followed the National Academy of Medicine established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 81 subjects from the CoFAR2 study and 84 subjects from the POISED study. All subject samples were analyzed using the BBEA methodology. The peanut BBEA test measures levels of two Ara h 2 epitopes and compares their combination to a pre=specified threshold. If the combination of the two epitope levels is at or below the threshold, then the subject is ruled Not Allergic, otherwise the subject is ruled Allergic. All allergic diagnoses were OFC confirmed and subject ages were 7-55 years. Results: In validation on the CoFAR2 and POISED cohorts, the peanut BBEA test had a combined sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy of 91%, 95%, 95%, 91%, 18.2, 0.09 and 93%, respectively. Conclusion: The peanut BBEA test performance in validation demonstrated overall high accuracy and compared very favorably with existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE and peanut component testing.