Differences in the DNA Methylome of T cells in Adults With Asthma of Varying Severity.

Background:DNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity or asthma endotypes are less well-defined. Objective:To examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation. Methods:Peripheral blood T cells from 35 adults with asthma in Beijing, China were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores. Results:Significant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway. Conclusion:These findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to the phenotype and severity of their overall disease.