Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 16, 2022; 10(26): 9254-9263
Published online Sep 16, 2022. doi: 10.12998/wjcc.v10.i26.9254
Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data
Sergey Morozov, Tatyana Sentsova
Sergey Morozov, Department of Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow 115446, Russia
Tatyana Sentsova, Department of Hospital Pediatrics No. 2, Russian National Research Medical University named after N.I. Pirogov, Moscow 117997, Russia
Author contributions: Morozov S and Sentsova T designed this study; Morozov S collected and analyzed the data, performed statistical analysis, and drafted the manuscript; all authors critically revised the manuscript and approved its final version.
Supported by Ministry of Science and Higher Education, No. FGMF-2022-0005 and No. 0410-2020-0007.
Institutional review board statement: The study was reviewed and approved by Ethic Committee of Federal Research Center of Nutrition and Biotechnology (No. 2, 06FEB2017).
Informed consent statement: All study participants provided written informed consent prior to study enrollment.
Conflict-of-interest statement: Dr. Morozov reports grants from Russian Science Foundation, personal fees from AstraZeneca, personal fees from AlfaSigma, non-financial support from Laborie, personal fees from DrFalk, personal fees from Takeda, from Federal Research Center of Nutrition and Biotechnology, outside the submitted work.
Data sharing statement: Technical appendix and dataset available from the corresponding author at reasonable request. Participants gave informed consent for anonymized data sharing.
STROBE statement: The authors have read the STROBE statement – checklist of items and the manuscript was prepared and revised according to STROBE statement – checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sergey Morozov, MD, PhD, Doctor, Senior Researcher, Department of Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition, Biotechnology and Food Safety, Kashirskoye shosse, 21, Moscow 115446, Russia. morosoffsv@mail.ru
Received: March 16, 2022
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
Processing time: 169 Days and 7.9 Hours
Abstract
BACKGROUND

Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease (GERD).

AIM

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Gastroesophageal reflux disease, Gene expression, Cytokines, Erosive esophagitis, Non-erosive gastroesophageal reflux disease, Esophageal multichannel intraluminal impedance-pH, Gastroesophageal reflux

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.