| Autor: |
Kiselev IS; Pirogov Russian National Research Medical University, Moscow, 117997 Russia.; National Medical Research Center for Cardiology, Moscow, 121552 Russia.; kiselev.ivan.1991@gmail.com., Kulakova OG; Pirogov Russian National Research Medical University, Moscow, 117997 Russia.; National Medical Research Center for Cardiology, Moscow, 121552 Russia., Danilova LV; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991 Russia.; Johns Hopkins School of Medicine, Baltimore, MD 21205 USA., Baturina OA; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia., Kabilov MR; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia., Popova EV; Pirogov Russian National Research Medical University, Moscow, 117997 Russia., Boyko AN; Pirogov Russian National Research Medical University, Moscow, 117997 Russia.; Federal Center for Brain and Neurotechnology, Federal Medical and Biological Agency of the Russian Federation, Moscow, 117997 Russia., Favorova OO; Pirogov Russian National Research Medical University, Moscow, 117997 Russia.; National Medical Research Center for Cardiology, Moscow, 121552 Russia. |
| Abstrakt: |
The pathogenesis of multiple sclerosis (MS), a chronic disease of the CNS, includes autoimmune and neurodegenerative components. In most cases, patients develop relapsing-remitting MS (RRMS), while 10-15% of patients develop primary progressive MS (PPMS), which differs from RRMS in the mechanisms of the pathological process, some demographic, and some clinical characteristics. These differences may be explained by the epigenetic regulation of gene expression in PPMS including DNA methylation as one of the key epigenetic processes. The features of DNA methylation in various cell populations in PPMS patients remain understudied. The goal of this study is to identify differentially methylated CpG sites (DMSs) of the genome of CD4+ T lymphocytes, which characterize PPMS. The study included eight treatment-naive PPMS patients and eight healthy controls. Genome-wide analysis of DNA methylation of CD4+ T lymphocytes was performed using high-density DNA microarrays. We have identified 108 DMSs, which distinguish PPMS patients from healthy controls. In PPMS patients 81% of the DMSs are hypermethylated. More than a half of the identified DMSs are located in known genes in CpG islands and adjacent regions, which indicates a high functional significance of these DMSs in PPMS development. Analysis of the overrepresentation of DMS-containing genes in the main biological processes demonstrates their involvement in the regulation of cell adhesion to the extracellular matrix and the development of the immune response, i.e., antigen processing and presentation, and development of the immune system. Genome-wide analysis of DNA methylation in CD4+ T lymphocytes of PPMS patients indicates the involvement of this epigenetic process in the immunopathogenesis of the disease. These results may help better understand the pathogenesis of this severe form of MS. |
