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A comprehensive transcriptome profiling in inclusion body myositis [RNA-Seq]

ABSTRACT: Gene expression profile of coding and non-coding RNA in IBM muscles.

ORGANISM(S): Homo sapiens

PROVIDER: GSE151757 | GEO | 2021/07/01

REPOSITORIES: GEO

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A comprehensive transcriptome profiling in inclusion body myositis [miRNA-Seq]

Project description:Profiling of miRNA RNA in IBM muscles.

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Project description:Myositis is characterised by muscle inflammation and weakness. Although generally thought to be driven by a systemic autoimmune response, increasing evidence suggests that intrinsic changes in the muscle might also contribute to the pathogenesis. Long non-coding RNAs (lncRNAs) are a family of novel genes that regulate gene transcription and translation. To determine the potential role of lncRNAs, we employed next generation sequencing to examine the transcriptome in muscle biopsies obtained from two histologically distinct patient populations, inclusion body myositis (IBM) and anti-Jo-1-associated myositis (Jo-1).

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Project description:Inclusion body myositis (IBM) is an autoimmune and degenerative disorder of skeletal muscle. The B cell infiltrates in IBM muscle tissue are predominantly fully differentiated antibody-secreting plasma cells, with scarce naïve or memory B cells. The role of this infiltrate in the disease pathology is not well understood. To better define the humoral response in IBM, we used adaptive immune receptor repertoire sequencing to generate large B cell receptor (BCR) repertoire libraries from IBM muscle biopsies and compared them to those generated from dermatomyositis (DM), polymyositis (PM), and circulating CD27+ memory B cells, derived from healthy controls and antibody secreting cells (ASC) collected following vaccination. The repertoire properties of the IBM infiltrate included: expanded clones that equaled or exceeded the highly clonal vaccine-associated ASC repertoire; reduced somatic mutation selection pressure in the complementary determining regions and framework regions; and enriched usage of class switched IgG and IgA isotypes, with a minor population of IgM expressing cells. These IBM IgM-expressing population revealed unique features, including an elevated somatic mutation frequency and distinct CDR3 physicochemical properties., These findings demonstrate that the IBM muscle BCR repertoire is highly distinct from DM and PM and circulating antigen-experienced subsets, suggesting that it may form through selection by a disease-specific set of antigens.

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Project description:We investigated the gene and exon espression profiling in muscle biopsies of patients affected by inclusion body myosistis, polymyositis and in normal muscle controls

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A comprehensive transcriptomic profiling in inclusion body myositis

Project description:A comprehensive transcriptomic profiling in inclusion body myositis

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Project description:A comprehensive transcriptome profiling in inclusion body myositis [RNA-Seq]

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Project description:The purpose of this study is to review recent scientific advances relating to the natural history, cause, treatment and serum and imaging biomarkers of inclusion body myositis (IBM).Several theories regarding the aetiopathogenesis of IBM are being explored and new therapeutic approaches are being investigated. New diagnostic criteria have been proposed, reflecting the knowledge that the diagnostic pathological findings may be absent in patients with clinically typical IBM. The role of MRI in IBM is expanding and knowledge about pathological biomarkers is increasing. The recent description of autoantibodies to cytosolic 5' nucleotidase 1A in patients with IBM is a potentially important advance that may aid early diagnosis and provides new evidence regarding the role of autoimmunity in IBM.IBM remains an enigmatic and often misdiagnosed disease. The pathogenesis of the disease is still not fully understood. To date, pharmacological treatment trials have failed to show clear efficacy. Future research should continue to focus on improving understanding of the pathophysiological mechanisms of the disease and on the identification of reliable and sensitive outcome measures for clinical trials. IBM is a rare disease and international multicentre collaboration for trials is important to translate research advances into improved patient outcomes.

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Project description:Purpose of reviewTo discuss recent developments in our understanding of epidemiology, diagnostics, biomarkers, pathology, pathogenesis, outcome measures, and therapeutics in inclusion body myositis (IBM).Recent findingsRecent epidemiology data confirms a relatively higher prevalence in the population aged above 50 years and the reduced life expectancy. Association with cancer and other systemic disorders is better defined. The role of magnetic resonance imaging (MRI) and ultrasound in diagnosis as well as in following disease progression has been elucidated. There are new blood and imaging biomarkers that show tremendous promise for diagnosis and as outcome measures in therapeutic trials. Improved understanding of the pathogenesis of the disease will lead to better therapeutic interventions, but also highlights the importance to have sensitive and responsive outcome measures that accurately quantitate change.SummaryThere are exciting new developments in our understanding of IBM which should lead to improved management and therapeutic options.

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