A MULTICENTER LONG-TERM COHORT STUDY OF EOSINOPHILIC ESOPHAGITIS VARIANTS AND THEIR PROGRESSION TO EOE OVER TIME

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: 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 six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastro-esophageal 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%; non-specific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (IQR 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, 62.2% year 6). Sequential RNA sequencing analyses revealed only seven genes associated with this progression (with TSG6 and ALOX15 among the top three upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6, 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). CONCLUSION: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes appear 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.

Original languageEnglish (US)
JournalClinical and translational gastroenterology
DOIs
StateAccepted/In press - 2024

Keywords

  • Dysphagia
  • esophageal eosinophilia
  • lymphocytic esophagitis
  • next generation RNA sequencing

ASJC Scopus subject areas

  • Gastroenterology

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