Dataset Information

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

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Dilollo J

PROVIDER: S-EPMC8502783 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits.ObjectiveTo determine the effects of environmental allergen sensitization on response to treatment in children with EoE in the southeastern United States.MethodsPatients 2 to 18 years old who were referred to the Arkansas Children's Hospital Eosinophilic Gastrointestinal Disorders Clinic from January 2012 to January 2016 were enrolled in a prospective, longitudinal cohort study with collection of demographics, clinical symptoms, medical history, allergy sensitization profiles, and response to treatment over time. Comparisons were made between complete responders (peak esophageal eosinophil count <15 per high-power field [HPF]) and nonresponders (>25 eosinophils per HPF) after treatment with diet elimination alone, swallowed corticosteroids alone, or diet elimination and swallowed corticosteroids. Sensitization patterns to environmental allergens found in the southeastern United States were analyzed for the effect on treatment response.ResultsA total of 223 individuals were enrolled. Of these, 182 had environmental allergy profiling and at least one endoscopy while receiving proton pump inhibitor (PPI) therapy. Twenty-nine individuals had PPI-responsive EoE and were excluded from further analysis, leaving 123 individuals with non-PPI-responsive EoE who were further analyzed; 72 (58.5%) were complete responders and 33 (26.8%) were nonresponders. Seventeen individuals (13.8%) were partial responders (≥1 but ≤25 eosinophils per HPF) and excluded from further analysis. Nonresponders were more likely to be sensitized to perennial allergens (P = .02). There was no significant difference in response based on seasonal allergen sensitization. Individuals with mold or cockroach sensitization were more likely to fail combination diet and swallowed corticosteroid treatment (P = .02 and P = .002).ConclusionPerennial allergen and mold sensitization may lead to nonresponse to EoE treatment in some patients. Additional studies are needed to further understand the effect of environmental allergens on EoE.Trial registrationClinicalTrials.gov identifier: NCT01779154.