Epigenetics. 2024 Dec;19(1):2289786. doi: 10.1080/15592294.2023.2289786.Epub 2023 Dec 13.

Samuel R Reynolds ¹, Lucas A Salas ¹, Ji-Qing Chen ¹, Brock C Christensen ^1 2

Author information

¹Department of Epidemiology, Geisel School of Medicine, Dartmouth College, NH, Lebanon, USA.

²Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, NH, Lebanon, USA.

Abstract

DNA methylation has been extensively utilized to study epigenetic patterns across many diseases as well as to deconvolve blood cell type proportions. This study builds upon previous studies examining methylation patterns in paediatric patients with varying stages of Crohn's disease to extend the immune profiling of these patients using a novel deconvolution approach. Compared with control subjects, we observed significantly decreased levels of CD4 memory and naive, CD8 naive, and natural killer cells and elevated neutrophil levels in Crohn's disease. In addition, Crohn's patients had a significantly elevated neutrophil-to-lymphocyte ratio. Using an epigenome-wide association approach and adjusting for potential confounders, including cell type, we observed 397 differentially methylated CpG (DMC) sites associated with Crohn's disease. The top genetic pathway associated with the DMCs was the regulation of arginine metabolic processes which are involved in the regulation of T cells.