Epigenetic variations and psychosocial parameters in relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is proposed to be a T cell mediated immune disease of the central nervous system involving the destruction of myelin surrounding the axons leading to progressive neurological damage. The symptoms of MS include motor and sensory disturbances, fatigue, depression and cognitive impairment. This thesis has two parts. The first is an observational study of early relapsing-remitting MS patients; cognitive tests (Paced Audio Serial Addition Test [PASAT] and Audio Recorded Cognition Screen [ARCS]) were used to monitor the cognitive function. Concurrently the mental health of patients was also examined. This observational study examined the impact of mental health on cognition in a cohort of early MS patients with little physical disability. The study confirmed that depression, anxiety and fatigue impact are strongly correlated with cognitive test scores of MS patients. This study has added another mental health parameter, stress. The levels of patients’ stress were associated with total ARCS score. The impact of treatment on mental health parameters was investigated but no difference was found. The second current study investigates the DNA methylation profile of CD4⁺ T cells, CD8⁺ T cells and CD19⁺ B cells of MS patients and healthy controls was investigated. There was a strong association between the MS risk gene HLA-DRB1 and the methylation profile for CD4⁺ T cells. There were associations with other MS risk genes including T cell receptor alpha (TCRA). The differential methylation profile for each immune cell subset was different with only CD4⁺ T cell having an association with MS risk genes. This was the first study to examine all 3 lymphocyte subsets DNA methylation in an MS cohort.