Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children

BACKGROUND: Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically. OBJECTIVE: To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation. METHODS: We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry. RESULTS: Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P <.001) and Ara h 2/total IgE ratios (r = 0.697; P <.001) and moderately with Arah2-sIgE diversity (r = 0.540; P <.001). On a linear regression model, Arah2-sIgE levels (standardized beta-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized beta-coefficient [ 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2. CONCLUSIONS: Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.