A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time
Year: 2024
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined. METHODS: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls. RESULTS: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months). DISCUSSION: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.
Authors: Thomas Greuter, Alex Straumann, Yuniel Fernandez-Marrero, Nina Germic, Aref Hosseini, Apinya Chanwangpong, Shida Yousefi, Dagmar Simon, Margaret H. Collins, Christian Bussmann, Mirna Chehade, Evan S. Dellon, Glenn T. Furuta, Nirmala Gonsalves, Ikuo Hirano, Fouad J. Moawad, Luc Biedermann, Ekaterina Safroneeva, Alain M. Schoepfer, Hans-Uwe Simon
Institutions: Centre Hospitalier Universitaire Vaudois, University Hospital Zurich, GZO Spital Wetzikon, University of Bern, University Hospital of Bern, Cincinnati Children's Hospital Medical Center, Icahn School of Medicine at Mount Sinai, University of North Carolina at Chapel Hill, Children's Hospital Colorado, University of Colorado Anschutz, University of Colorado Denver, Northwestern University, Scripps Clinic, Medizinische Hochschule Brandenburg Theodor Fontane
Language: English
Topic: Eosinophilic Esophagitis
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
Funders: National Science Foundation, Bristol-Myers Squibb, AstraZeneca, Sanofi, Celgene, Danone, Novartis Foundation, American Partnership for Eosinophilic Disorders, Regeneron Pharmaceuticals, Campaign Urging Research for Eosinophilic Disease, Rare Diseases Clinical Research Network, Eosinophilic Family Coalition, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Novartis Stiftung für Medizinisch-Biologische Forschung, Dr. Falk Pharma, Norgine, Genentech, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G2678175721, G2976362549, G3500416612, G3893463699, G481745248, G4913822037, Defining clinically meaningful therapeutic endpoints in Eosinophilic Esophagitis, Molecular pathways regulating eosinophil numbers and functions, SYNECTIN PROMOTES LIVER FIBROSIS BY INCREASING PDGFRa SIGNALING IN VITRO AND IN VIVO, G947216580
OpenAlex ID: W4391565941