title: Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression.
abstract: BACKGROUND
  The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown.
  
  
  OBJECTIVE
  To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment.
  
  
  METHODS
  In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids.
  
  
  RESULTS
  Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI-REE, at both oesophageal sites (P ≤ 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers.
  
  
  CONCLUSIONS
  Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Molina-Infante
authors.forename: M D
authors.initials: MD
authors.lastname: Rivas
authors.forename: M
authors.initials: M
authors.lastname: Hernandez-Alonso
authors.forename: G
authors.initials: G
authors.lastname: Vinagre-Rodríguez
authors.forename: J M
authors.initials: JM
authors.lastname: Mateos-Rodríguez
authors.forename: C
authors.initials: C
authors.lastname: Dueñas-Sadornil
authors.forename: B
authors.initials: B
authors.lastname: Perez-Gallardo
authors.forename: L
authors.initials: L
authors.lastname: Ferrando-Lamana
authors.forename: N
authors.initials: N
authors.lastname: Fernandez-Gonzalez
authors.forename: R
authors.initials: R
authors.lastname: Bañares
authors.forename: J
authors.initials: J
authors.lastname: Zamorano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics; D015536:Down-Regulation; D004802:Eosinophilia / Q000188:drug therapy / Q000235:genetics*; D057765:Eosinophilic Esophagitis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; C578095:IL13 protein, human; C508599:IL5 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; D054328:Proton Pump Inhibitors