IgE to epitopes of Ara h 2 enhance the diagnostic accuracy of Ara h 2-specific IgE.

Alexandra F Santos,Henry T Bahnson,Soheila J Maleki,Colin O’Rourke,Gideon Lack,Hsiaopo Cheng,Matthew Kwok,Barry K Hurlburt,Hannah J Gould,Sneha Ramaswamy,Louisa James,Oliver Hemmings,Nuno L Barbosa‐Morais,Brian J Sutton

doi:10.1111/all.14301

Abstract

Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy. To identify differences in IgE and IgG4 binding to peanut peptides between peanut-allergic (PA) and peanut-sensitized but tolerant (PS) children. PA (n=56), PS (n=42) and nonsensitized nonallergic (NA, n=10) patients were studied. Synthetic overlapping 15-mer peptides of peanut allergens (Ara h 1-11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood-ratio tests between each specified nominal logistic regression models. Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2-specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. Ara h 2 peptide-specific IgE added diagnostic value to Ara h 2-specific IgE. Ability of peptide-specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance.

Highlights

Allergen-specific IgE is necessary but not sufficient for the development of allergic reactions to a food allergen
We previously showed that the levels of IgG4 to peanut were higher in peanutsensitized but tolerant (PS) compared to peanut allergic (PA) patients but it was the relative amount of IgG4 compared to IgE in individual patients, i.e. the
Most patients were sensitized to the three major peanut allergens Ara h 1-3 (Table E4)

Summary

Introduction

Allergen-specific IgE is necessary but not sufficient for the development of allergic reactions to a food allergen. Kingdom have detectable specific IgE to peanut and only 2.6% are peanut allergic as confirmed by double-blind placebo-controlled food-challenge (DBPCFC)[1] This discrepancy between allergic sensitization and clinical reactivity poses diagnostic difficulties and raises fundamental questions about the mechanisms of food allergy and oral tolerance. Many cases can be found of PS patients who eat peanut without developing any symptoms and have relatively higher levels of P-sIgE compared to PA patients who develop allergic reactions, often severe, when exposed to peanut This is the case when considering specific IgE to Ara h 2, which has proved to be discriminative between allergic and tolerant individuals[3]. Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy

Methods

Results

Discussion

Conclusion