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Updated: Jul 13, 2025
Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
Published on: May 10, 2024
A synthesis and subgroup analysis of the eosinophilic esophagitis tissue transcriptome
Justin Jacobse1, Rachel Brown2, Frank Revetta3
1Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands; Division of Molecular Pathogenesis, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Veterans Affairs Tennessee Valley Health Care System, Nashville, Tenn.
Background:
Eosinophilic esophagitis (EoE) is a chronic immune mediated inflammatory disorder of the esophagus. It is still unknown why children and adults present differently, and there is little evidence about why it is more common in men than women.
Objective:
Our aim was to synthesize published and unpublished esophageal bulk RNA-sequencing (RNA-seq) data to gain novel insights into the pathobiology of EoE and examine the differences in EoE transcriptome by sex and age group.
Methods:
Esophageal bulk RNA-seq data from 5 published and 2 unpublished studies resulting in 137 subjects (EoE: N = 76; controls: N = 61) were analyzed. For overall analysis, combined RNA-seq data of patients with EoE were compared with those of controls and subgroup analysis was conducted in patients with EoE by age of the patient (children [<18 years] vs adults [≥18 years]) and sex (female vs male). Gene-set enrichment analysis, ingenuity pathway analysis (IPA), cell-type analysis, immunohistochemistry, and T-cell or B-cell receptor analysis were performed.
Results:
Overall analysis identified dysregulation of new genes in EoE compared with controls. IPA revealed that EoE is characterized by a mixed inflammatory response compared with controls. Cell-type analysis showed that cell composition varied with age: children had more mast cells, whereas adults had more macrophages. Finally, gene-set enrichment analysis and IPA revealed pathways that were differentially regulated in adults versus children and male versus female patients with EoE.
Conclusions:
Using a unique approach to analyze bulk RNA-seq data, we found that EoE is characterized by a mixed inflammatory response, and the EoE transcriptome may be influenced by age and sex. These findings enhance insights into the molecular mechanisms of EoE.
