Published online Sep 16, 2022. doi: 10.12998/wjcc.v10.i26.9254
Peer-review started: March 16, 2022
First decision: April 10, 2022
Revised: April 21, 2022
Accepted: August 12, 2022
Article in press: August 12, 2022
Published online: September 16, 2022
Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease (GERD).
To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis (EE) and non-erosive forms of GERD (NERD) and its association with data of esophageal multichannel intraluminal impedance-pH (MII-pH) measurements.
This was a single-center prospective study. Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy. Expression of interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor α (TNFA), toll-like receptor 4 (TLR4), GATA binding protein 3 (GATA3), differentiation cluster 68 (CD68) and β-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays. MII-pH measurements were performed on all the participants. Diagnosis of GERD was confirmed by the results of the MII-pH data. Based on the endoscopy, patients were allocated to the groups of EE and NERD. The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results. We used nonparametric statistics to compare the differences between the groups. Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.
Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis. Higher expression of IL-18 (5.89 ± 0.4 vs 5.28 ± 1.1, P = 0.04) and GATA3 (2.92 ± 0.86 vs 2.23 ± 0.96, P = 0.03) was found in the EE group compared to NERD. Expression of IL-1β, IL-18, TNFA, and TLR4 was lower (P < 0.05) in the control group compared to EE and NERD. Esophageal acid exposure correlated with the expression of IL-1β (Spearman’s rank r = 0.29), IL-18 (r = 0.31), TNFA (r = 0.35), GATA3 (r = 0.34), TLR4 (r = 0.29), and CD68 (r = 0.37). Mean esophageal рН correlated inversely with the expression of IL-18, TNFA, GATA3, TLR4, and CD68. No association of gene expression with the number of gastroesophageal refluxes was found.
In patients with EE, local expression of IL-18 and GATA3 was higher compared to subjects with NERD. Esophageal acid exposure correlated directly with expression of IL-1β, IL-18, TNFA, TLR4, CD68, and β-2 microglobulin genes. Inverse correlation was revealed between expression of IL-18, TNFA, GATA3, TLR4, and CD68 and mean esophageal pH.
Core Tip: Local expression of cytokines may be involved in pathophysiology of different forms of gastroesophageal reflux disease. We found a different profile of local expression of cytokines in subgroups of patients with erosive esophagitis and non-erosive forms of gastroesophageal reflux disease. For the first time we have revealed a correlation between gene expression of interleukin-18, tumor necrosis factor alpha, GATA binding protein 3, toll-like receptor 4, differentiation cluster 68 and mean esophageal pH and an association of acid exposure with expression of interleukin-1β, interleukin-18, tumor necrosis factor alpha, toll-like receptor 4, differentiation cluster 68 and β-2 microglobulin.