Esophageal mucosal mast cell density and degranulation are increased in gastroesophageal reflux disease

Gastroesophageal 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. Distal esophageal biopsies were collected from healthy control subjects (HC; n = 10) and subjects with functional heartburn (FH; n = 9), nonerosive reflux disease (NERD; n = 13), and erosive reflux disease (ERD; n = 12). Immunohistochemistry was used to visualize tryptase expression in the esophageal mucosa. The localization of tryptase+ mast cells was identified as intraepithelial or papillary, and the degranulation state of individual mast cells was determined based on the tryptase staining pattern. There was an increased density of mast cells in the esophageal papillae and epithelium of patients with ERD compared with HCs. The density of degranulated intraepithelial mast cells was significantly higher in subjects with FH and subjects with ERD compared with HCs, with a trend toward an increase in NERD. In NERD and ERD, the density of degranulated mast cells in papillae was significantly higher than in HCs. In FH, the density of intraepithelial mast cells positively correlated with reflux disease questionnaire (RDQ) score. Mast cells are more numerous in the esophageal mucosa of subjects with ERD, and activity is increased in subjects with FH, NERD, and ERD. This could contribute to mucosal inflammation, barrier dysfunction, and visceral hypersensitivity in patients with GERD. Future studies should investigate the role of mucosal mast cells in GERD, representing a possible future treatment target.NEW & NOTEWORTHY This is the first study to characterize mast cell localization and degranulation in subjects with pH-phenotyped FH, NERD, and ERD compared with healthy controls, showing elevated mast cell numbers in ERD, with increased degranulation in all patient groups (FH, NERD, and ERD). These findings suggest that mast cell activation may contribute to mucosal inflammation and symptom generation in GERD, particularly FH.