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

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 (TH ) 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 TH 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 TH -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 TH lymphocytes most accurately predicts clinical EoE milk allergy.

Development of the Child- and Parent-Rated Scales of Food Allergy Anxiety (SOFAA).

BACKGROUND: Anxiety can be excessive and impairing in children with food allergy (FA). There is no accepted condition-specific measure of anxiety for this population. OBJECTIVE: To evaluate the validity and reliability of new child- and parent-rated measures of FA-related anxiety in youth. METHODS: Items for the Scale of Food Allergy Anxiety (SOFAA) were developed by a cognitive-behavioral therapist specializing in pediatric anxiety, in consultation with FA medical professionals and parents of children with FA. Dyads (n = 77) of children with FA (aged 8-18 years; 42.9% females) and their parents (95.5% females) completed full versions of the SOFAA (21 items; scored 0-4) via online survey. RESULTS: The child-rated SOFFA-C mean score was 29.1 ± 18.3; the parent-rated SOFAA-P mean score was 33.9 ± 16.1. Higher scores indicate higher reported anxiety. Coefficient alphas were 0.94 and 0.92. Factor analyses and item-response theory analyses supported the creation of the 14-item SOFAA-C-brief and the 7-item SOFAA-P-brief, accounting for 93% and 79% of total variance, respectively. Correlations revealed strong convergence between child- and parent-report for both the full (r = 0.85) and brief (r = 0.79) versions. Correlations with a generic measure of child anxiety (Screen for Child Anxiety Related Disorders) and the Food Allergy Quality of Life Questionnaire ranged from moderate to strong, whereas those with a generic measure of child eating problems (About Your Child's Eating) were weak to moderate, supporting convergent and divergent validity. Scores of 48 dyads who completed SOFAAs at time 2 (mean, 16.0 days) appeared stable over time, supporting test-retest reliability. CONCLUSIONS: The 21-item SOFAA-C and SOFAA-P are reliable and valid scales for measuring condition-specific anxiety in youth with FA. As shorter screening measures, the SOFAA-C-brief and the SOFAA-P-brief are also reliable and valid.