Project description:DNA methylation profiling of NeuN+sorted neuronal nuclei from post-mortem brain tissue of Multiple Sclerosis (MS) patients (n=10) (MS) and non-neurological controls (n=7) (non-MS). Genomic DNA was subjected to conventional BS-treatment as well as oxidative BS (oxBS)-conversion using TrueMethylTM 96 kit of CEGXTM (Cambridge Epigenetix Limited) to allow for subsequent detection of hydroxymethylation (5hmC = BS - oxBS).
Project description:This SuperSeries is composed of the following subset Series: GSE17393: Transcription signature of Multiple Sclerosis in peripheral blood mononuclear cells. GSE17409: Pregnancy changes expression in peripheral blood mononuclear cells of healthy donors GSE17410: Pregnancy changes expression in peripheral blood mononuclear cells of Multiple Sclerosis (MS) patients Refer to individual Series
Project description:Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.
Project description:Background Despite compelling evidence that cigarette smoking impacts the risk of developing Multiple Sclerosis (MS), little is known about smoking-associated changes in the primary exposed cells in the lung of patients. We aimed to examine molecular changes occurring in pulmonary immune cells from MS patients in relation to smoking and in comparison to healthy controls (HC). Methods We profiled genome-wide DNA methylation (5mC) and hydroxymethylation (5hmC) in bronchoalveolar lavage (BAL) cells collected from female MS patients (9 smokers, 8 non-smokers) and healthy volunteers (10 smokers, 12 non-smokers), using Illumina Infinium EPIC arrays on conventional (BS) and oxidative (oxBS) bisulfite DNA. We profiled gene expression using RNA-sequencing in non-smoker MS patients and controls. Findings The most prominent changes were found in relation to smoking, with 1376 BS-differentially methylated positions (DMPs), 131 5mC-DMPs and 4 5hmC-DMP (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. To further explore MS-specific signature, we performed RNA sequencing in BAL cells from non-smoker MS patients and controls. Overall, methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle but concordant changes associated to genes connected to reduced transcriptional/translational processes and enhanced cellular adhesion and migration, further corroborating findings from animal studies. Interpretation Our study provides new insights into the impact of smoking on lung inflammation in the immunopathogenesis of MS. -