Epigenetic methylation in Eosinophilic Esophagitis: Molecular ageing and novel biomarkers for treatment response

Abstract

Background: Treatment failure in eosinophilic esophagitis (EoE) is common. We hypothesize that DNA methylation differs between patients by treatment response to topical steroids (oral viscous budesonide), thus offering the potential to inform targeting therapies. Objective: We sought to identify differentially methylated sites and affiliated genes in pre-treatment oesophageal cells between responders and non-responders and test for accelerated epigenetic ageing in oesophageal cells of EoE patients. Methods: DNA was extracted from prospectively collected and biobanked oesophageal biopsies from 36 Caucasian treatment naïve EoE patients at diagnosis. Methylation assays were completed using the Infinium HumanMethylation450 BeadChip. Normalized β values for each CpG site were tested (t test) for differential methylation. Further, 353 CpG probes were used to estimate epigenetic age for each patient and a linear regression model tested whether chronologic age and epigenetic age differed. Epigenetic age results were confirmed in an independent cohort of healthy controls. Results: Eighteen CpG sites were differentially methylated by treatment response (P < .00001). The mean epigenetic age and chronological age were 56.1 ± 11.1 and 36.7 ± 12.3 years, a mean age difference of 19.3 ± 5.2 years (P < .0001); accelerated ageing was not observed in the oesophageal cells of healthy controls. Conclusions and clinical relevance: EoE patients that respond versus do not respond to treatment have differences in their methylation profile, including enrichment of genes in pathways consistent with cellular injury and repair due to environmental stress and cell adhesion and barrier integrity. EoE also appears to accelerate cellular ageing. Whether treatment can arrest or reverse accelerated epigenetic ageing and the implications for long-term disease progression is important areas for future research.

Non–IgE- or Mixed IgE/Non–IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis

“…The role of epigenetics in this field has been specifically demonstrated for IgE food allergies, but a similar effect might also be hypothesized for non-IgE food allergies. Different DNA methylation profiles were in fact recently demonstrated between patients with EoE who responded to treatment in comparison with non-responders [ 178 ], suggesting that epigenetic modifications may also be biomarkers of treatment response in some non-IgE mediated food allergies.…”

Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis

“…Prediction of treatment response related to tCS is an area of active research. Nonresponse has been associated with esophageal dilation (42–44), severe esophageal narrowing (45), increased BMI (30), younger age (31,44), and molecular features (46,47). In our analysis, the lower response rate in non-Whites persisted despite adjusting for these other known factors related to tCS response.…”

Actualización en el manejo terapéutico de la esofagitis eosinofílica en adultos

“…En relación con las terapias moleculares, no existe suficiente evidencia, sin embargo, en el estudio de Jensen et al (Jensen et al, 2020) se ha atribuido a la resistencia al tratamiento, se evidenció que los pacientes que no responden adecuadamente tienen una hipermetilación a nivel los codones CpG, por lo tanto, esta podría ser una diana terapéutica a futuro.…”