Peripheral markers of allergen-specific immune activation predict clinical allergy in eosinophilic esophagitis.

Abstract

Eosinophilic esophagitis (EoE) is a T-cell-mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE-causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen-specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E-mediated milk allergy (n = 9). We measured total and milk-specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4⁺ T helper (T_H ) cell proliferation and cytokine production after stimulation with endotoxin-depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches. Total and milk-specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused T_H lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL-4⁺ of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk-dependent memory T_H -cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL-4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy. Peripheral markers of allergen-specific immune activation may be useful in identifying EoE-causal foods. Assaying milk-dependent IL-4 production by circulating memory T_H lymphocytes most accurately predicts clinical EoE milk allergy.