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Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro.TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P.001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r = 0.34-0.47, P.001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P.001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling.Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

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.