Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients

Holly A Morrison; Kacie J Hoyt; Christina Mounzer; Hannah M Ivester; Barrett H Barnes; Bryan Sauer; Emily C McGowan; Irving C Allen

doi:10.3389/falgy.2023.1239273

Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients

Front Allergy. 2023 Aug 24:4:1239273. doi: 10.3389/falgy.2023.1239273. eCollection 2023.

Authors

Holly A Morrison^#¹, Kacie J Hoyt^#¹, Christina Mounzer¹, Hannah M Ivester², Barrett H Barnes³, Bryan Sauer⁴, Emily C McGowan^{5

6}, Irving C Allen^{1

2

7}

Affiliations

¹ Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
² Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States.
³ Division of Pediatric Gastroenterology/Nutrition, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, United States.
⁴ Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
⁵ Division of Allergy and Clinical Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
⁶ Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁷ Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, VA, United States.

^# Contributed equally.

Abstract

Introduction: Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development.

Methods: We used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity.

Results: Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE (CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7). In addition, we identified differential expression of several genes from the MUC and SPRR families, which have been limited in previous reports.

Discussion: Our findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, SPRR and MUC, that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.

Keywords: epidermal differentiation complex; epithelial barrier; human esophageal biopsy; keratinization; mucin.

Grants and funding

This work was supported by the Virginia Maryland College of Veterinary Medicine (I.C.A.); the Virginia Tech Carilion School of Medicine (I.C.A.); National Institute of Allergy and Infectious Diseases (NIAID): K23AI123596 (E.C.M) and R21AI151497 (E.C.M); The National Center for Advancing Translational Sciences (iTHRIVE): UL1TR003015 (E.C.M. & I.C.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of any funding agency.