Multiple Sclerosis Pattern II Demyelinating Lesions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA259871 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1561742.fastq.gz | Fastqsanger.gz | |||
| SRR1561743.fastq.gz | Fastqsanger.gz | |||
| SRR1561744.fastq.gz | Fastqsanger.gz |
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Project description:Multiple sclerosis 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 infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination. Examination of 3 different demyelinating lesions identified by Immunohistopathology.
2016-07-03 | E-GEOD-60942 | biostudies-arrayexpress
Project description:Multiple sclerosis 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 infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination.
2016-01-01 | GSE60942 | 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: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:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-03 | E-GEOD-60943 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-01-01 | GSE60943 | GEO
Project description:Canine distemper virus (CDV)-induced demyelinating leukoencephalitis (CDV-DL) in dogs is a translational animal model for human demyelinating diseases such as multiple sclerosis. The aim of this study was to perform an assumption-free microarray analysis of gene expression in different subgroups of CDV-DL as compared to normal controls. Dogs were classified into normal controls (group 1), acute CDV-DL lesions with CDV within the brain but without demyelination and inflammation (group 2), subacute lesions with demyelination but without inflammation (group 3), and subacute to chronic lesions with demyelination and inflammation (group 4).
2014-04-23 | E-MEXP-3917 | biostudies-arrayexpress
Project description:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by increased inflammation and immune responses, oxidative injury, mitochondrial dysfunction, and iron dyshomeostasis leading to demyelination and axonal damage. In MS, incomplete remyelination results in chronically demyelinated axons and degeneration coinciding with disability. This suggests a failure in the ability to remyelinate in MS, however, the precise underlying mechanisms remain unclear. We aimed to identify proteins whose expression was altered in chronic inactive white matter lesions and periplaque white matter in MS tissue to reveal potential pathogenic mechanisms. Laser capture microdissection coupled to proteomics was used to interrogate spatially preserved changes in formalin-fixed paraffin-embedded brain tissue from chronic MS individuals and controls with no apparent neurological complications. Histopathological maps guided the capture of inactive lesions, periplaque white matter, and cortex from chronic MS individuals along with corresponding white matter and cortex from control tissue. Label free quantitation by liquid chromatography tandem mass spectrometry was used to discover differentially expressed proteins between the various brain regions. In addition to confirming loss of several myelin-associated proteins known to be affected in MS, proteomics analysis of chronic inactive MS lesions revealed alterations in myelin assembly, metabolism, and cytoskeletal organization. Notably, a subset of proteins that were altered in MS white matter indicate altered lipid metabolism. Our findings highlight proteome changes in chronic inactive MS white matter lesions and periplaque white matter, which may be crucial for proper myelinogenesis, bioenergetics, focal adhesions, and cellular function. These findings highlight the importance and feasibility of spatial approaches such as laser capture microdissection-based proteomics analysis of pathologically distinct regions of MS brain tissue. Identification of spatially resolved changes in the proteome of MS brain tissue should aid in the understanding of pathophysiological mechanisms and the development of novel therapies.
2024-08-29 | PXD047800 | Pride
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:Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS), where ongoing demyelination and remyelination failure are the major factors for progressive neurological disability. In this report, we employed a comprehensive proteomic approach and immunohistochemical (IHC) validation to gaininsight into the pathobiological mechanisms that may be associated with the progressive phase of MS disease. Isolated proteins from myelinated regions, demyelinated white matter lesions (WMLs), and grey-matter lesions (GMLs) of well-characterized progressive MS brain tissues were subjected to label-free quantitative mass spectrometry (LFQ-MS). Using a system-biology approach, we detected increased expression of proteins belonging to mitochondrial electron transport complexes and oxidative phosphorylatio pathway in WMLs. Intriguingly, many of these proteins and pathways had opposite expression patterns in GMLs of progressive MS brains. A comparison to the huma MitoCarta database mapped the mitochondrial proteins to mitochondrial subunits in both WMLs and GMLs. Taken together, we provide evidence of opposite expression of mitochondrial proteins in response to demyelination of white- and grey-matter regions in progressive MS brain.
2021-12-21 | PXD029285 | Pride