DNA Methylation Profile of CD14+ Monocytes Changes in Primary Progressive Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system, characterized by significant clinical heterogeneity. In 10–15% of patients, primary progressive MS (PPMS) develops, in which, unlike the most common relapsing-remitting form of MS, neurodegeneration steadily progresses and, as a consequence, neurological symptoms continuously increase. Peculiarities of epigenetic regulation of gene expression may be one of the reasons for the differences in the pathogenesis of two MS forms. DNA methylation is one of the key epigenetic mechanisms that remains almost unexplored in different cell populations of PPMS patients. The aim of this work was to identify differential methylation profiles of CpG sites in the CD14+ monocyte DNA that characterize PPMS. Genome-wide analysis of DNA methylation in PRMS patients and healthy individuals identified 169 differentially methylated positions (DMPs), 90.5% of which were hypermethylated in PRMS patients. More than half of all DMPs are located in/near known genes and within CpG islands and their neighboring regions, which indicates their high functional significance. We found six differentially methylated regions (DMRs) in genes OR2L13, CAT, LCLAT1, HOXA5, RNF39, and CRTAC1 involved in inflammation and neurodegeneration, which indicates active epigenetic regulation of their expression.