Introduction: Gastro-esophageal reflux disease (GERD) is a chronic condition encompassing visceral pain - experienced as heartburn and, in some cases, inflammation of the esophageal mucosa. Although mast cell dysregulation has been described in disorders of gut-brain interaction, it has been understudied in GERD. We aimed to characterize mast cell localization and degranulation in GERD esophageal mucosa. Methods: Distal esophageal biopsies were collected from healthy control (HC; N=10), functional heartburn (FH; N=9), non-erosive reflux disease (NERD; N=13), and erosive reflux disease (ERD; N=12) subjects. Immunohistochemistry was used to visualize tryptase expression in the esophageal mucosa. The localization of tryptase+ mast cells were identified as intraepithelial or papillary, and the degranulation state of individual mast cells was determined based on tryptase staining pattern. Results: There was an increased density of mast cells in the esophageal papillae and epithelium of ERD patients compared to HCs. The density of degranulated intraepithelial mast cells was significantly higher in FH and ERD subjects compared to HCs, with a trend towards increase in NERD. In NERD and ERD, the density of degranulated mast cells in papillae was significantly higher than HCs. In FH, density of intraepithelial mast cells positively correlated with RDQ score. Conclusions: Mast cells are more numerous in the esophageal mucosa of ERD subjects, and activity is increased in FH, NERD, and ERD subjects. This could contribute to mucosal inflammation, barrier dysfunction, and visceral hypersensitivity in GERD patients. Future studies should investigate the role of mucosal mast cells in GERD, representing a possible future treatment target.
Leech et al. (Tue,) studied this question.