Abstract | BACKGROUND: Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery. OBJECTIVE: In this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities. METHODS: We evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE. RESULTS: The EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis ( eotaxin 3, CCL26), barrier molecules ( desmoglein 1, DSG1), tissue remodeling ( periostin, POSTN), and mast cells ( carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment. CONCLUSION: These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.
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Authors | Ting Wen, Evan S Dellon, Fouad J Moawad, Glenn T Furuta, Seema S Aceves, Marc E Rothenberg |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 135
Issue 1
Pg. 187-97
(Jan 2015)
ISSN: 1097-6825 [Electronic] United States |
PMID | 25441638
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Adolescent
- Adult
- Child
- Child, Preschool
- Computational Biology
- Eosinophilia
(drug therapy, genetics, immunology)
- Esophagus
(immunology)
- Female
- Gastroesophageal Reflux
(drug therapy, genetics, immunology)
- Gene Expression Profiling
- Humans
- Hypersensitivity
(drug therapy, genetics, immunology)
- Inflammation
(drug therapy, genetics, immunology)
- Male
- Middle Aged
- Proton Pump Inhibitors
(therapeutic use)
- Young Adult
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