Persistent Esophageal Changes Following Histologic Remission in Eosinophilic Esophagitis.
EoE transcriptome
Eosinophilic esophagitis
diagnostic panel
eosinophil
inflammatory memory
molecular diagnostics
predictive medicine
remission
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
26 Dec 2023
26 Dec 2023
Historique:
received:
21
07
2023
revised:
27
11
2023
accepted:
19
12
2023
medline:
29
12
2023
pubmed:
29
12
2023
entrez:
28
12
2023
Statut:
aheadofprint
Résumé
Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood and therefore chronic EoE-directed therapy is required to prevent long-term sequelae. We investigated if with EoE patients in histologic remission have persistent dysregulation of esophageal gene expression. Esophageal biopsies from pediatric (n=51) and adult (n=52) subjects with EoE in histopathologic remission (<15 eos/HPF) and control (n=48 pediatric, n=167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE Diagnostic Panel (EDP), a set of 94 esophageal transcripts differentially expressed in active EoE. Defining remission as <15 eosinophils/HPF, we identified 511 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (FDR < 0.05). Using the stringent definition of remission (0 eos/HPF), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (FDR ≤ .05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the Endoscopic Reference Score (Spearman r= 0.35, p= 0.011), specifically correlating with the rings EREFS subscore (r= 0.53, p=0.004). We have identified persistent EoE-associated esophageal gene expression in patients with deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE.
Sections du résumé
BACKGROUND
BACKGROUND
Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood and therefore chronic EoE-directed therapy is required to prevent long-term sequelae.
OBJECTIVE
OBJECTIVE
We investigated if with EoE patients in histologic remission have persistent dysregulation of esophageal gene expression.
METHODS
METHODS
Esophageal biopsies from pediatric (n=51) and adult (n=52) subjects with EoE in histopathologic remission (<15 eos/HPF) and control (n=48 pediatric, n=167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE Diagnostic Panel (EDP), a set of 94 esophageal transcripts differentially expressed in active EoE.
RESULTS
RESULTS
Defining remission as <15 eosinophils/HPF, we identified 511 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (FDR < 0.05). Using the stringent definition of remission (0 eos/HPF), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (FDR ≤ .05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the Endoscopic Reference Score (Spearman r= 0.35, p= 0.011), specifically correlating with the rings EREFS subscore (r= 0.53, p=0.004).
CONCLUSION
CONCLUSIONS
We have identified persistent EoE-associated esophageal gene expression in patients with deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE.
Identifiants
pubmed: 38154664
pii: S0091-6749(23)02545-9
doi: 10.1016/j.jaci.2023.12.012
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023. Published by Elsevier Inc.