Epigenomic and lipidomic changes in Multiple Sclerosis patients with high Body Mass Index enhance the neurotoxic function of monocytes

The growing obesity “epidemic” has shed light on its negative impact on overall health status, not only in relation to cardiovascular disorders and metabolic syndrome, but also in regard to its influence on a variety of other health conditions, including autoimmune diseases, such as Multiple Sclerosis (MS). High Body Mass index (BMI) is a risk factor for MS, however, it is not known whether and how it could impact disease course. Several studies, including those on the Dutch Famine, have highlighted the role of epigenetic modifications in mediating phenotypic changes in response to metabolic shifts, suggesting that epigenetic changes could be a potential mechanism for BMI-driven differences in disease course. Using the Illumina 450K array, we identified genome-wide differences in DNA methylation between blood monocytes from therapy-naïve RRMS patients with high BMI compared to low BMI. Differences were subtle, however, were heavily skewed in the positive direction in the high BMI group, indicative of overall DNA hypermethylation. Further curation of differentially methylated genes, using stringent criteria, revealed enrichment in anti-inflammatory functions among the top hypermethylated genes. Thus, epigenomic changes related to inflammatory processes of monocytes are detected in MS patients with high BMI compared to those with low BMI and could potentially impact disease course by modulating immune-driven neurotoxicity. 23 Multiple Sclerosis patients with high Body Mass Index (25 and over) and 26 Multiple Sclerosis patients with low Body Mass Index (under 25) were recruited for the study. Monocytes were isolated from the blood of patients using CD14 beads and DNA extracted and bisulfite converted from the sorted cells. Genome-wide DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.