Usha Krishnan1, Chan Lijuan2, Gifford J Andrew3, Marc E Rothenberg4, Ting Wen5. 1. Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Paediatric Gastroenterology, Sydney Children's Hospital, Sydney, Australia. 2. Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia. 3. Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Anatomical Pathology (SEALS), Prince of Wales Hospital, Sydney, Australia. 4. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 5. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: ting.wen@cchmc.org.
Abstract
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.
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.
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