Granzyme B is elevated in esophageal biopsies from children with eosinophilic esophagitis.

Helena Thulin, Jesper Säfholm, Joachim Lundahl, Viktor Jovic, Mikael Adner, Caroline Nilsson

Journal: Journal of pediatric gastroenterology and nutrition 2024;78(2):313-319

PMID: 38374566

Abstract

OBJECTIVES

Eosinophilic esophagitis (EoE) is an immune-mediated antigen-triggered inflammatory disease of the esophagus. Our aim was to investigate inflammatory responses by an ex vivo biopsy provocation-based method, stimulating biopsies with milk, wheat, and egg extracts.

METHODS

An experimental study was conducted on esophageal biopsies from children who underwent esophagogastroduodenoscopy. Supernatants were collected before and after stimulation of the biopsies with food extracts and analyzed for 45 different inflammatory markers. Biopsies were also stained for histological analyzes.

RESULTS

Study subjects included 13 controls, 9 active EoE, and 4 EoE in remission, median age 12 years. Of the 45 markers analyzed, three had significant differences between controls and patients with active EoE, Granzyme B, (GzmB), IL-1ra, and CXCL8 (p < .05). Levels of GzmB were higher, and levels of IL-1ra were lower in patients with active EoE compared with controls and EoE in remission both at baseline and after food extract stimulation. CXCL8 increased in active EoE compared with controls only after stimulation. The number of histologically detected GzmB-positive cells were significantly higher in patients with active EoE in contrast to control and EoE remission (p < .05).

CONCLUSIONS

The levels of the barrier-damaging protease GzmB were higher in the supernatant both before and after stimulation with food extract ex vivo in patients with active EoE. GzmB was also observed histologically in biopsies from patients with active EoE. The presence of elevated serine protease GzmB in esophageal mucosa of children with active EoE suggests a role in the pathogenesis of this disorder.

© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Address: Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.; Astrid Lindgren Children's Hospital, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden.; Experimental Asthma and Allergy Research, Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Medical Diagnostics, Karolinska University Hospital, Stockholm, Sweden.; Department of Clinical Pathology and Cytology, Karolinska University Laboratory, Stockholm, Sweden.; Sachs Children and Youth Hospital, Department of Pediatric Allergology and Pulmonology, South Hospital, Stockholm, Sweden.
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