+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation



Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation



Journal of Allergy and Clinical Immunology 135(1): 187-197



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. 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. 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. 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. 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.

(PDF emailed within 0-6 h: $19.90)

Accession: 059155113

Download citation: RISBibTeXText

PMID: 25441638

DOI: 10.1016/j.jaci.2014.08.043


Related references

Eosinophilic esophagitis versus proton pump inhibitor-responsive esophageal eosinophilia: Transcriptome analysis. Journal of Allergy and Clinical Immunology 139(6): 2010-2013.E4, 2017

Case report of proton pump inhibitor responsive esophageal eosinophilia: why 2 months of proton pump inhibitors is required. Diseases of the Esophagus 29(6): 700-703, 2017

Proton pump inhibitors partially restore mucosal integrity in patients with proton pump inhibitor-responsive esophageal eosinophilia but not eosinophilic esophagitis. Clinical Gastroenterology and Hepatology 12(11): 1815-23.E2, 2015

Clinicopathologic Analysis of Proton Pump Inhibitor-Responsive Esophageal Eosinophilia in Korean Patients. Gut and Liver 10(1): 37-41, 2016

Proton-pump inhibitor-responsive esophageal eosinophilia. Current Opinion in Gastroenterology 30(4): 428-433, 2015

Proton Pump Inhibitor-Responsive Esophageal Eosinophilia. Gastroenterology and Hepatology 10(11): 739-741, 2014

Proton pump inhibitor-responsive esophageal eosinophilia: still a valid diagnosis?. Current Opinion in Gastroenterology 33(4): 285-292, 2017

Markers of eosinophilic inflammation for diagnosis of eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia: a prospective study. Clinical Gastroenterology and Hepatology 12(12): 2015-2022, 2015

Proton pump inhibitor-responsive esophageal eosinophilia does not preclude food-responsive eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 137(2): 631-633, 2016

Proton pump inhibitor-responsive esophageal eosinophilia: A new entity in search of recognition?. Revista de Gastroenterologia de Mexico 81(2): 113-115, 2017

Proton Pump Inhibitor-Responsive Esophageal Eosinophilia: Controversies and Its Clinical Implications. Gut and Liver 10(1): 1-2, 2016

Proton pump inhibitor responsive esophageal eosinophilia, a distinct disease entity?. World Journal of Gastroenterology 20(30): 10419-10424, 2015

Proton pump inhibitor-responsive esophageal eosinophilia: a historical perspective on a novel and evolving entity. Revista Espanola de Enfermedades Digestivas 107(1): 29-36, 2016

Histologic similarities in children with eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. Journal of Allergy and Clinical Immunology 2018, 2018

Proton Pump Inhibitor-responsive Esophageal Eosinophilia: An Overview of Cases from One University Hospital Center. Korean Journal of Gastroenterology 67(4): 178-182, 2017