Gene expression in immortalized B-lymphocytes derived from patients with multiple sclerosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10064 | GEO | 2008/05/08
SECONDARY ACCESSION(S): PRJNA108167
REPOSITORIES: GEO
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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: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: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).
2019-06-21 | GSE119532 | 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:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by antibody and complement deposition. MS is considered a prototypic T cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Here, we used next generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions and subsequently isolated these as T cell clones from autologous cerebrospinal fluid. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T cell infiltrate in pattern II brain lesions. Our data provide the first functional evidence for a role of Th2/Tc2 cells in pattern II MS.
2016-01-01 | GSE60914 | GEO
Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by antibody and complement deposition. MS is considered a prototypic T cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Here, we used next generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions and subsequently isolated these as T cell clones from autologous cerebrospinal fluid. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T cell infiltrate in pattern II brain lesions. Our data provide the first functional evidence for a role of Th2/Tc2 cells in pattern II MS. Two stimulated CD4+ Th2 brain infiltrating T cell clones compared with stimulated circulaiting memory CD4+ T cells and two stimulated CD8+ T cell clones (one Tc1 and one Tc2) compared with each other.
2016-07-03 | E-GEOD-60914 | biostudies-arrayexpress
Project description:This project aims at the detection of specific patterns of miRNAs in peripheral blood samples of MS patients. As controls, blood of donors without known affection have been tested. Using the miRNA patterns we hope to detect a diagnostic pattern for the non-invasive diagnosis of MS. In this study, we compared 20 Multiple Sclerosis samples to 21 control samples using the sanger miRBAse 12.0 miRNA biochip manufactured by febit. Samples were analyzed with the Geniom Realtime Analyzer (GRTA, febit gmbh, Heidelberg, Germany) using the Geniom Biochip miRNA homo sapiens. Each array contains 7 replicates of 866 miRNAs and miRNA star sequences as annotated in the Sanger miRBase 12.0. To benchmark the platform, we tested technical replicates using bought total RNA of brain and liver samples (ambion), achieving a correlation of 0.97.
2010-06-25 | E-GEOD-17846 | biostudies-arrayexpress
Project description:A method to stimulate T lymphocytes with a broad range of brain antigens would facilitate identification of the autoantigens for multiple sclerosis and enable definition of the pathogenic mechanisms important for multiple sclerosis. In previous work we found the obvious approach of culturing leukocytes with homogenized brain tissue does not work because the brain homogenate suppresses antigen-specific lymphocyte proliferation. We now report a method that substantially reduces the suppressive activity. We used this non-suppressive brain homogenate to stimulate leukocytes from multiple sclerosis patients and controls. We also stimulated with common viruses for comparison. We measured proliferation, selected the responding CD3+ cells with flow cytometry, and sequenced their transcriptomes for mRNA and T cell receptor sequences. The mRNA expression suggested the brain-responding cells from MS patients are potentially pathogenic. The T cell receptor repertoire of the brain-responding cells was clonal with minimal overlap with virus antigens.
2022-01-13 | GSE193260 | GEO