Differential CpG methylation in peripheral naive and memory CD4+T-cells, and monocytes in early rheumatoid arthritis patients

The genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation and many T-cells genes with a strong MHC-association, pointing to immuno-genetic mechanisms as disease triggers. We aim to identify methylation change in naive and memory CD4+T-cells and monocytes in the early stage of disease, to gain insight to disease pathology. DNA-methylation was explored using a genome wide array (DNA methylation Illumina 450K bead chip array). Differential methylation in promoters of many genes was associated with several disease relevant pathways notably in naive CD4+T-cells. This pointed to the IL6/JAK1/STAT3 signalling cascade linking into inflammatory mechanisms and TNF signalling as well as the engagement of naive CD4 T-cells intoTh17 differentiation and the implication of several Interferon response genes. 10 early RA patients and 6 Healthy controls were selected. PBMC were sorted for 3 cell subsets: naive CD4+T-cells, memory CD4+T-cells, and monocytes. DNA was extracted from each sample, then bisulfite converted and used on an Illumina Infinium 450k Human Methylation array: 46 methylation profiles were retained after quality controls assessments.