The characterization of circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveals differences across clinically diagnosed myositis subsets
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247816 | GEO | 2024/11/14
REPOSITORIES: GEO
Similar Datasets
Project description:Objectives: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Materials and methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis (IBM) and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic. Results Analysis of differentially expressed genes showed that interferon signalling and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM (n=5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target (ADK, CD28 and SLC4A10) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK. Conclusion: MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM.
2019-07-31 | GSE125977 | GEO
Project description:Objectives: This study aimed to investigate the association between immunoglobulin G (IgG) N-glycosylation patterns and the clinical endotypes of patients with idiopathic inflammatory myopathies (IIM), potentially informing disease classification and therapeutic target identification. Methods: We recruited 168 IIM patients and 52 healthy controls, and performed IgG N-glycosylation profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employed GlycoQuant for intact glycopeptide analysis. Clinical data were extracted, and statistical analyses were conducted to correlate glycosylation profiles with clinical manifestations. Unsupervised clustering analysis was applied to identify novel IIM subgroups based on differential IgG N-glycosylation. Results: Our analysis revealed significant disparities in IgG N-glycosylation between IIM patients and controls, with 13 specific glycoforms exhibiting marked alterations. The level of fucosylated glycans was significantly higher in the IIM patients than healthy controls. Three distinct IIM endotypes were identified, each characterized by unique glycosylation signatures and clinical phenotypes. These endotypes were not congruent with conventional diagnostic subgroups and demonstrated associations with various clinical outcomes, including muscle weakness, interstitial lung disease (ILD), and serological profiles.
2024-12-03 | PXD058502 |
Project description:Objective: In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods: Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNM-NM-3 expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions: Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition. Investigation of constitutive and immunoproteasomal subunit expression in muscle tissue of patients with inflammatory and non-inflammatory myopathies These transcriptomes were used as reference signatures of different immune cell types in order to estimate the contribution of immune cell transcripts to the muscle transcriptomes investigated in the datasets GSE2044, GSE3112, GSE5370, GSE39454, GSE3307, GSE13205, GSE10685.
2014-06-04 | E-GEOD-58173 | biostudies-arrayexpress
Project description:The characterization of circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveals differences across clinically diagnosed myositis subsets
| PRJNA1040779 | ENA
Project description:Objective: In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods: Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNγ expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions: Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition.
2014-06-04 | GSE58173 | GEO
Project description:Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of autoimmune disorders affecting skeletal muscle, including dermatomyositis (DM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Polymyositis with mitochondrial pathology (PM-Mito) has been proposed as a potential IIM subtype, with emerging evidence suggesting it may represent an early form of IBM. IBM is characterized by unique clinical features, such as insidious onset and resistance to immunotherapies, alongside hallmark histopathological findings, including rimmed vacuoles, cytoplasmic protein aggregates, CD8+ T cell-dominated inflammation, and prominent mitochondrial abnormalities. Mitochondrial dysfunction, ragged-red fibers, and disrupted oxidative phosphorylation are increasingly recognized as central contributors to IBM pathology, implicating mitochondrial processes in both muscle weakness and chronic inflammation.
This study presents a longitudinal and cross-sectional proteomic analysis of IBM in comparison to other IIM subtypes. We identified both established and novel hallmarks of IBM, particularly highlighting mitochondrial dysfunction and immune dysregulation, while also examining PM-Mito as a potential precursor state to IBM. Using an unbiased mass spectrometry-based proteomic approach, we identified a distinct proteomic signature for IBM characterized by mitochondrial alterations and type II interferon-associated immune pathway dysregulation. PM-Mito samples displayed a dysregulation of immune regulatory proteins and mitochondrial pathways. This study reinforces the unique molecular profile of IBM compared to other IIM subtypes while strengthening the concept of a disease continuum between IBM and PM-Mito. By uncovering shared mitochondrial and immune dysregulation in IBM and PM-Mito, these findings support the notion that PM-Mito may represent an early or transitional stage of IBM, providing new insights into disease progression and potential therapeutic targets.
2026-05-12 | PXD063841 | JPOST Repository
Project description:The role of TIGIT in idiopathic inflammatory myopathies
| PRJNA1148962 | ENA
Project description:Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies
| PRJNA600019 | ENA
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Project description: Not available
| S-EPMC6880850 | biostudies-literature