J Allergy Clin Immunol Pract. 2024 May 18:S2213-2198(24)00529-4. doi: 10.1016/j.jaip.2024.05.015. Online ahead of print.
ABSTRACT
BACKGROUND: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood.
OBJECTIVE: We examined the correlation of a validated, patient-reported outcome (PRO) metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis.
METHODS: Data were extracted from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Patients were subgrouped by esophageal dilation history. We compared a validated PRO 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 utilized single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms.
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 non-epithelial cells and 3 in epithelial cells; during histologic remission, only 4/11 (36%) non-epithelial versus 3/3 (100%) epithelial genes had decreased expression to <50% of that in active EoE. Fibroblasts expressed 5/11 (45%) non-epithelial EEsAI-associated EDP genes. A subset of non-epithelial (8/11, 73%), but not EoE-representative (0/4, 0%; CCL26, CAPN14, DSG1, SPINK7), genes was upregulated in patients with EoE with the highest versus lowest symptom burden.
CONCLUSION: The correlation of symptoms and non-epithelial esophageal gene expression substantiates that non-epithelial cells (e.g., fibroblasts) likely contribute to symptom severity.
PMID:38768900 | DOI:10.1016/j.jaip.2024.05.015
