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.
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: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).
Project description:The aim of this study was to identify differentially expressed genes in peripheral blood mononuclear cells from MS patients that were responders or non-responders to the neuroantigen myelin basic protein. Using microarray we measured mRNA-expression levels in freshly isolated peripheral blood mononuclear cells from 17 untreated patients with multiple sclerosis. Based on studies, measuring the responses of blood derived T-cells to myelin basic protein ex vivo, these 17 untreated MS-patients can be divided into two groups: 4 of the untreated multiple sclerosis patients had T-cells that responded to myelin basic protein ex vivo whereas 13 untreated MS patients had T-cells that did not respond to myelin basic protein ex vivo.
Project description:Multiple sclerosis (MS) is a chronic and progressive neurological disease. MS is characterized by early-stage neuroinflammation, neurodegeneration, and demyelination, with a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. The currently unsatisfied availability of diagnostic and prognostic biomarkers concerning disease progression and treatment response represents an important requirement for therapy individualization and drug efficacy. Specific Disease Therapies (DMTs) are available to prevent MS-related brain damage; however, the specific drug choice is still under debate and needs further characterization. Since differentially expressed miRNAs have been proposed as diagnostic tools in neurodegenerative/neuro-inflammatory diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, we characterized the miRNA expression profiling in peripheral blood mononuclear cells (PBMC) of subjects with relapsing-remitting MS treated with high efficacy DMTs: Cladribine (CLA, n=11 patients) or Ocrelizumab (OCRE, n=14 patients). The treated patients were compared to control (CTR) untreated subjects (n=15). Blood samples were collected from patients before treatment (time t0) and 6 months post-treatment (time t1), but just once from control subjects. CLA drug tablets were administered to the selected relapsing-remitting MS patients with a dosage of 1.75 mg/kg given for 5 days. OCRE drug was administered to the other relapsing-remitting MS patients by infusion with a dosage of 300 mg, twice in two weeks.