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Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis.
- Source :
-
The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2024 May 18. Date of Electronic Publication: 2024 May 18. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Background: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood.<br />Objective: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis.<br />Methods: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms.<br />Results: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden.<br />Conclusion: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity.<br /> (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2213-2201
- Database :
- MEDLINE
- Journal :
- The journal of allergy and clinical immunology. In practice
- Publication Type :
- Academic Journal
- Accession number :
- 38768900
- Full Text :
- https://doi.org/10.1016/j.jaip.2024.05.015