Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis

Caterina Strisciuglio,Alessandra Vitale,Felicity Payne,Komal Nayak,Matthias Zilbauer,Marialuisa Andreozzi,Erasmo Miele

doi:10.1186/s13148-021-01072-y

Abstract

Eosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers.

Highlights

Eosinophilic esophagitis (EoE) is a chronic, allergic/ immune-mediated inflammatory disease and the leading cause of dysphagia and food impaction in children as well as adults [1]
Principal component analyses (PCA) of genome-wide DNA methylation profiles revealed a distinct separation of esophageal biopsies obtained from children newly diagnosed with EoE (n = 7) from healthy controls (n = 13, Fig. 1a)
Performing unsupervised clustering analysis further confirmed the presence of disease-associated DNA methylation signatures in patients diagnosed with EoE compared to healthy controls as clear clusters emerge that separate EoE patient from the majority of control samples (Fig. 1c)

Summary

Introduction

Eosinophilic esophagitis (EoE) is a chronic, allergic/ immune-mediated inflammatory disease and the leading cause of dysphagia and food impaction in children as well as adults [1]. (See figure on page.) Fig. 1 a Principal components plot (PC1, PC2) depicting patient diagnosis with number of eosinophils per high-powered field (eos/hpf ) in controls (n = 13), and in EoE patients at diagnosis (EoE T0, n = 6) and after treatment (EoE T1, n = 5) after quality control. C Clustering of EoE patients at diagnosis (T0) and non-EoE controls (total n = 19) in all CpGs passing quality control using Pearson’s correlation with average clustering. E Heatmap of all samples after quality control, excluding outliers but including biological duplicates (n = 29) subset for the top 25 CpGs significantly differentially methylated between EoE patients at diagnosis (T0) and non-EoE controls (FDR p < 0.01 and Δβ ≥|0.05|) using Pearson’s correlation with average clustering.

Methods

Results

Conclusion