Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression

BackgroundThe molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown. AimTo compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment. MethodsIn consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and >15eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40mg b.d. for 8weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids. ResultsFifty 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 (P0.008), 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 41.79eos/HPF, P=0.025) and led to symptom remission in 16%, but did not influence Th2 markers. ConclusionsBaseline 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.