A GWAS of Progression in Multiple Sclerosis
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ABSTRACT:
PROVIDER: EGAS00001007162 | EGA |
REPOSITORIES: EGA
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Project description:Background: Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives. Methods: A multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients. Results: MS neither predisposes nor protects from the development of gliomas. Patients with glioblastoma WHO grade 4 without isocitratdehydrogenase (IDH) mutations have a longstanding history of MS, whereas patients diagnosed with IDH-mutant astrocytoma WHO grade 2 receive multiple sclerosis diagnosis mostly at the same time or later. Concurrent MS is associated with a lesser extent of tumor resection and a worse prognosis in IDH-mutant glioma patients (PFS 32 vs. 64 months, p=0.0206). When assessing tumor-intrinsic differences no distinct subgroup-defining methylation pattern is identified in gliomas of MS patients compared to other glioma samples. However, differential methylation of immune-related genetic loci including human leukocyte antigen locus on 6p21 and interleukin locus on 5q31 is found in MS patients vs. matched non-MS patients. In line, inflammatory disease activity increases in 42% of multiple sclerosis patients after brain tumor radiotherapy suggesting a susceptibility of multiple sclerosis brain tissue to pro-inflammatory stimuli such as ionizing radiation. Conclusions: Concurrent low-grade gliomas should be considered in multiple sclerosis patients with slowly progressive, expansive T2/FLAIR lesions. Our findings of typically reduced extent of resection in MS patients and increased MS activity after radiation may inform future treatment decisions.
2023-12-27 | GSE243465 | GEO
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.
2019-12-17 | GSE135511 | GEO
Project description:Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterised by myelin loss and progressive neurodegeneration. To better understand MS lesion initiation and progression, we generated spatial gene activity maps of white (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detected novel transcriptional domains, including an identifiable rim around active WM lesions. These active lesion rims were characterised by changes in astrocytic, oligodendrocytic, and microglial gene activity. Furthermore, we identified three novel WM lesion trajectories, predicting how normal appearing WM could progress into WM lesions, with lesion rims, active lesion cores, and mixed active/inactive lesion cores as potential outcomes. Our findings offer new insights into MS lesion progression, and the dynamic molecular and cellular processes that underlie MS.
2024-08-05 | GSE208747 | GEO
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
2010-01-10 | E-GEOD-17449 | biostudies-arrayexpress
Project description:Affymetrix GeneChip Human Gene 1.0 ST Array was applied to compare the expression profiles in peripheral blood mononuclear cells(PBMC) between healthy controls and multiple sclerosis patients(MS pt). It suggested that certain genes involved in apoptosis pathway have been changed regulated in PBMC from MS pt. Applying Affymetrix GeneChip Human Gene 1.0 ST Array and the mixed effects model for gene set analysis, we compared gene expression profiles between 8 multiple sclerosis (MS) patients and 4 healthy controls (HC).
2011-03-01 | E-GEOD-23832 | biostudies-arrayexpress
Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the brain. Among characteristics of MS pathology are cortical grey matter abnormalities, which have been linked to clinical signs such as cognitive impairment. To understand MS cortical grey matter pathogenesis, we performed differential gene expression analysis of MS normal appearing grey matter (NAGM) and control grey matter. HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of grey matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression. Our data indicate that increased HLA-DRB1 expression in the brain of MS patients may be an important factor in how the HLA-DR15 haplotype contributes to MS risk in the target organ.
2020-01-13 | GSE131281 | GEO
Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the brain. Among characteristics of MS pathology are cortical grey matter abnormalities, which have been linked to clinical signs such as cognitive impairment. To understand MS cortical grey matter lesion pathogenesis, we performed differential gene expression analysis of MS cortical normal-appearing grey matter (NAGM) and grey matter lesions. HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of grey matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression. Our data indicate that increased HLA-DRB1 expression in the brain of MS patients may be an important factor in how the HLA-DR15 haplotype contributes to MS risk in the target organ.
2020-01-13 | GSE131279 | GEO
Project description:We measured global mRNA expression in peripheral blood mononuclear cells (PBMC) from 182 individuals, comprising of 142 multiple sclerosis (MS) patients affected with distinct MS clinical forms and 40 healthy controls.
2017-09-30 | E-MTAB-4890 | biostudies-arrayexpress
Project description:We measured global mRNA expression in peripheral blood mononuclear cells (PBMC) from 76 individuals, comprising of 49 multiple sclerosis (MS) patients affected with distinct MS clinical forms and 27 healthy controls.
2017-09-30 | E-MTAB-5151 | biostudies-arrayexpress
Project description:Human serum samples from Multiple Sclerosis (MS) subjects and healthy control subjects were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. Other neurodegenerative and non-neurodegenerative diseases were also used to help measure the specificity of the selected biomarkers.
2017-07-26 | GSE95718 | GEO