# Molecular and epigenetic predictors and mechanisms of treatment response to topical steroids in eosinophilic esophagitis

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $116,505

## Abstract

Molecular and epigenetic predictors and mechanisms of treatment response to topical steroids in
eosinophilic esophagitis
ABSTRACT
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease defined by abnormal infiltration of
eosinophils into the esophageal mucosa, leading to dysphagia, progressive esophageal stenosis, and food
impaction. The incidence and prevalence are rising dramatically, and EoE has rapidly become a major cause
of upper gastrointestinal morbidity. Despite this increasing importance, much is unknown about the ideal
approach to treatment, and we cannot predict which patients will respond to specific treatments. Practitioners
must frustratingly use trial and error, and patients are subjected to expensive therapies and invasive and costly
follow-up procedures without knowing their individual likelihood of response. While swallowed/topical
corticosteroids are currently a mainstay of therapy for EoE, non-response is common and can be seen in up to
50% of EoE patients. Identifying which patients are less likely to have a histologic response would allow for
personalization of therapy, but no predictors have been validated for clinical use. We have begun to address
this major knowledge gap, and now have promising data for two novel techniques. The first is differential
correlation of gene expression, where the correlation between gene pairs is assessed between responders and
non-responders. We identified a 22 gene module where there was significantly higher differential correlation in
non-responders at baseline prior to treatment, and also identified potential associated miRNA pathway
regulators. The second is epigenetic methylation, where we identified differential methylation at 18 CpG sites
when comparing treatment responders and non-responders at baseline. Because differential correlation and
methylation both imply differential regulation of biologic pathways, they can provide highly needed information
about molecular mechanisms of non-response, and also may yield new treatment targets. The overall goal of
the proposed study is to validate these two novel methods for prediction of treatment response in EoE and use
these results to investigate molecular mechanisms of non-response The specific aims are to 1) validate a pre-
treatment differential correlation gene expression module for prediction of topical steroid non-response in
patients with EoE; and 2) to validate a pre-treatment epigenetic methylation profile for prediction of topical
steroid non-response in patients with EoE. To achieve these aims, we will perform a secondary analysis of a
rich clinical and biosample set from an NIH-funded randomized clinical trial conducted by the PI (R01
DK101856) that compared budesonide to fluticasone for initial treatment of EoE. This innovative, hypothesis-
driven, and rigorously designed study will be conducted by an existing multidisciplinary team with recognized
expertise in EoE, clinical trials, epidemiology, genetics, statist...

## Key facts

- **NIH application ID:** 10150852
- **Project number:** 5R21DK122297-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Evan Samuel Dellon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $116,505
- **Award type:** 5
- **Project period:** 2020-04-27 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150852

## Citation

> US National Institutes of Health, RePORTER application 10150852, Molecular and epigenetic predictors and mechanisms of treatment response to topical steroids in eosinophilic esophagitis (5R21DK122297-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10150852. Licensed CC0.

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