Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia.
EoE transcriptome
Eosinophils
GERD
T(H)2 inflammation
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:
04 2019
04 2019
Historique:
received:
01
05
2018
revised:
20
07
2018
accepted:
24
08
2018
pubmed:
12
12
2018
medline:
24
4
2020
entrez:
12
12
2018
Statut:
ppublish
Résumé
A high prevalence of eosinophilic esophagitis (EoE) has been preliminarily reported in patients after repair of esophageal atresia (EA), but the basis of this association is unknown. We aimed to (1) characterize the EoE transcriptome in patients with EA, (2) compare the EoE transcriptome in patients with EoE and EA with that in patients with EoE alone, and (3) identify transcripts that could predispose patients with EA to EoE. This single-center, population-based, retrospective study identified 4 EoE study cohorts: healthy control subjects, patients with EA and EoE (EA+EoE+), patients with EA without EoE (EA+EoE-), and patients with EoE without EA (EA-EoE+). Molecular signatures were assessed by using the EoE diagnostic panel, a 94-gene expression quantitative PCR array. In a cohort of 110 pediatric patients with surgically repaired EA, 20 (18%) patients were given a diagnosis of EoE, representing a 364-fold enrichment of EoE in patients with EA compared with the general pediatric population. EoE diagnostic panel analyses revealed a major overlap between the EA+EoE+ and EA-EoE+ cohorts. A proportion (approximately 25%) of EoE signature genes were dysregulated in patients with EA+EoE- compared with healthy control subjects, including those involved in epithelial barrier function and type 2-associated inflammatory responses. Patients with EA+EoE+ exhibit a more severe EoE clinical phenotype than those with EA-EoE+ in terms of dysphagia and dilation need. Patients with EA have increased risk of EoE. Patients with EoE with EA have a similar molecular profile compared with that of patients with EoE without EA. Dysregulated baseline epithelial barrier and type 2-associated genes in EA monomorbidity might explain the higher EoE prevalence in patients with EA.
Sections du résumé
BACKGROUND
A high prevalence of eosinophilic esophagitis (EoE) has been preliminarily reported in patients after repair of esophageal atresia (EA), but the basis of this association is unknown.
OBJECTIVES
We aimed to (1) characterize the EoE transcriptome in patients with EA, (2) compare the EoE transcriptome in patients with EoE and EA with that in patients with EoE alone, and (3) identify transcripts that could predispose patients with EA to EoE.
METHODS
This single-center, population-based, retrospective study identified 4 EoE study cohorts: healthy control subjects, patients with EA and EoE (EA+EoE+), patients with EA without EoE (EA+EoE-), and patients with EoE without EA (EA-EoE+). Molecular signatures were assessed by using the EoE diagnostic panel, a 94-gene expression quantitative PCR array.
RESULTS
In a cohort of 110 pediatric patients with surgically repaired EA, 20 (18%) patients were given a diagnosis of EoE, representing a 364-fold enrichment of EoE in patients with EA compared with the general pediatric population. EoE diagnostic panel analyses revealed a major overlap between the EA+EoE+ and EA-EoE+ cohorts. A proportion (approximately 25%) of EoE signature genes were dysregulated in patients with EA+EoE- compared with healthy control subjects, including those involved in epithelial barrier function and type 2-associated inflammatory responses. Patients with EA+EoE+ exhibit a more severe EoE clinical phenotype than those with EA-EoE+ in terms of dysphagia and dilation need.
CONCLUSIONS
Patients with EA have increased risk of EoE. Patients with EoE with EA have a similar molecular profile compared with that of patients with EoE without EA. Dysregulated baseline epithelial barrier and type 2-associated genes in EA monomorbidity might explain the higher EoE prevalence in patients with EA.
Identifiants
pubmed: 30527929
pii: S0091-6749(18)31292-2
doi: 10.1016/j.jaci.2018.08.040
pmc: PMC6461044
mid: NIHMS1015714
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1455-1464.e2Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI045898
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI070235
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001425
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124355
Pays : United States
Informations de copyright
Copyright © 2018. Published by Elsevier Inc.
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