TRANSCRIPTOMIC RESPONSES TO DIETARY ELIMINATION IN EOSINOPHILIC ESOPHAGITIS (EOE) ACROSS ADULT AND PEDIATRIC POPULATIONS

Abstract

Introduction

Eosinophilic esophagitis (EoE) is a dietary antigen-mediated disease affecting children and adults. Numerous studies demonstrate the role of diet-elimination therapy in managing EoE; however, the mechanisms underlying diet therapy are poorly understood.

Methods

We performed bulk RNA-seq on esophageal biopsies of pediatric (N=33) and adult patients (N=44) diagnosed with EoE before and after dietary elimination, and after food reintroduction.

Results

We establish EoE, Adult and Pediatric scores that distinguish controls from active EoE patients and adult EoE from pediatric EoE patients. These scores were validated using public datasets. The Pediatric and EoE scores partially overlapped with the EoE Diagnostic Panel (EDP), while the Adult score (28 genes) did not. Pathway analysis on the Adult score revealed upregulation of NK-mediated immunity and down-regulation of intermediate filament organization. We observe transcriptional differences in diet-responsive EoE patients and develop a 52-gene age-independent Diet Response score. The Diet Response score decreased in diet-responsive patients following food avoidance, increased with food reintroduction and discriminated diet responders from non-responders prior to therapy. While 13 genes in the Diet Response score were shared with the EDP score, 39 genes were unique. Diet non-responsive adult EoE patients showed no significant changes in this score.

Conclusion

Our study represents the first comparative analysis of RNA-seq data from children and adults who responded to diet elimination therapy for EoE. We discovered unique transcriptional signatures specific to adult EoE and a Diet Response score unaffected by age. These findings hold promise for predicting individual responses to diet therapy in EoE patients.