Tu1870 Characteristics of Nighttime Reflux Assessed Using Multi-Channel Intraluminal Impedance pH Monitoring and a Portable Electroencephalograph

Background: Patients with untreated celiac disease (CD) often complain of reflux symptoms, which in 30% of cases are considered moderate to severe (CGH 2011; 9: 214-9).The glutenfree diet leads to a rapid and persistent improvement in reflux symptoms and most cases do not require the use of proton pump inhibitors.The mechanisms involved in the expression of reflux symptoms in CD patients are unknown.Objective: We explored symptomatic and mucosal markers of permeability of the lower esophagus in patients with newly diagnosed CD at the time of diagnostic endoscopy, patients with symptoms of GERD but no CD (GERD controls) and healthy controls without symptoms (healthy controls: HC).Methods: A cohort of 23 consecutive patients with active CD at the time of diagnosis, 5 GERD control patients, and 11 HC subjects, were enrolled in the study.Nine out of 23 CD patients had GERD symptoms considered as moderate or severe (>2 points in the GSRS questionnaire).Endoscopic biopsies from the distal esophagus were obtained 2 cm above the z-line.Samples were assessed for histological damage, dilated intercellular space (DIS) scores by optical microscopy (OM) and electron microscopy (EM), and tight junction (TJ) mRNA expression for zonnula occludens-1 (ZO-1) and claudin-2 and -3 (CL-2; CL-3) using Real Time qRT-PCR.Results: Patients with active CD had increased DIS scores compared to HC subjects (OM: 8.0±3.1 vs. 2.2±2.5;p<0.003 and EM: 31.7±9.5 vs. 15.0±5.1;p<0.04) but similar to GERD controls.CD patients without GERD symptoms also had higher DIS scores compared to HC (OM: p<0.006;EM: p<0.03) but similar to those in CD patients with GERD symptoms.Overall CD patients had lower expression of ZO-1 than HC (CD patients with and without GERD symptoms: p<0.003 and p>0.05; respectively).A non-statistical trend for higher CL-2 and CL-3 expression was observed in CD patients compared with GERD controls and no differences were detected between CD subgroups with or without GERD symptoms.CD patients had similar expression of CL-2 and CL-3 compared to HC. Conclusions: Our study suggests an impairment of mucosal permeability in the distal esophagus of patients with active CD irrespective of the presence of GERD symptoms.The altered expression of ZO-1, and CL-2 and CL-3 may underlie loss of TJ integrity in the esophageal mucosa, an expression pattern that is reminiscent of intestinal permeability abnormalities observed in CD, and that may contribute to reflux symptom expression and its reversion by the glutenfree diet.