Premium
Proton pump inhibitor‐responsive oesophageal eosinophilia correlates with downregulation of eotaxin‐3 and Th2 cytokines overexpression
Author(s) -
MolinaInfante J.,
Rivas M. D.,
HernandezAlonso M.,
VinagreRodríguez G.,
MateosRodríguez J. M.,
DueñasSadornil C.,
PerezGallardo B.,
FerrandoLamana L.,
FernandezGonzalez N.,
Bañares R.,
Zamorano J.
Publication year - 2014
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12914
Subject(s) - eotaxin , medicine , eosinophilia , eosinophilic esophagitis , dysphagia , gastroenterology , proton pump inhibitor , omeprazole , cytokine , eosinophil , disease , surgery , asthma
Summary 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. Aim 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.