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:
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.
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
Research background

Gastroesophageal reflux disease (GERD) has a number of manifestations, including erosive esophagitis (EE) and non-erosive form of GERD (NERD). Similar levels of intraesophageal acidity are often found in subjects with EE and NERD and little is known about the reasons.

Research motivation

Several reports suggest involvement of inflammatory cytokines in the pathogenesis of different forms of GERD. Local inflammatory response of the esophageal mucosa to gastroesophageal reflux (GER) may depend on gene expression of cytokines. However, data on the dependence of the expression on esophageal acidity are still lacking.

Research objectives

The objective of the study was to explore gene expression of inflammatory cytokines in esophageal mucosa in patients with EE and NERD and its association with data of esophageal multichannel intraluminal impedance-pH measurements.

Research methods

The data were obtained in a single-center prospective study. We analyzed the expression of interleukin (IL)-, 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 samples obtained during endoscopy. All the subjects underwent multichannel intraluminal impedance-pH measurements. Based on the presence of abnormal results, they were allocated either to the GERD group or to the control group. The GERD group was further divided into the EE group and the NERD group. Spearman’s rank correlation analysis was used to analyze association of cytokine expression with esophageal acidity and number and types of GER.

Research results

We found higher expression of IL-18 and GATA3 genes in the EE group compared to the NERD group. 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), and TLR4 (r = 0.29), CD68 (r = 0.37). Mean esophageal pH correlated inversely with the expression of IL-18, TNFA, GATA3, TLR4, and CD68. No association of the gene expression with number of GER was found.

Research conclusions

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. An inverse correlation was revealed between the expression of IL-18, TNFA, GATA3, TLR4, and CD68 and mean esophageal acidity. Expression levels of IL-10 did not differ significantly in the studied groups and did not correlate with esophageal acid exposure and number of GER.

Research perspectives

Larger studies are necessary to confirm the obtained results. Assessment of the association of the local inflammatory response with concentration of bile acids within the refluxate seems promising.