Circulating miR-150 in CSF is a novel candidate biomarker for multiple sclerosis

Bergman, Petra; Piket, Eliane; Khademi, Mohsen; James, Tojo; Brundin, Lou; Olsson, Tomas; Piehl, Fredrik; Jagodic, Maja

doi:10.1212/nxi.0000000000000219

Cited by 96 publications

(75 citation statements)

References 40 publications

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“…Similarly to miR-21, miR-150 modulates immune response and is functionally impaired in immune-mediated diseases which frequently co-exists with PBC (Bergman et al 2016;Chen et al 2017). MiR-150 shapes the maturation of T cells, B cells, and NK cells via direct downregulation of cMyb, a modulator of hematopoietic cells biology (Bezman et al 2011;Liu et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis

Wasik

Kempińska-Podhorodecka

Bogdanos

et al. 2020

Mol Med

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Background & Aims: Anti-mitochondrial-autoantibodies (AMA) remain a hallmark of Primary Biliary Cholangitis (PBC) however approximately 10% of patients test negative for these antibodies. They do not differ in terms of biochemistry or clinical presentation from AMA positive ones. Epigenetics play a key role in immune signalling. Two microRNAs (miRs), namely, miR-21 and miR-150 are known to be involved in liver inflammation and fibrosis. The expression of those two microRNAs and their downstream targets were analyze in the context of AMA-status and the stage of liver fibrosis. Methods: The relative levels of miR-21 and miR-150 and their target genes: cMyb, RAS-guanyl-releasing protein-1(RASGRP1), and DNA-methyltransferase-1(DNMT1) were determined by Real-Time PCR in serum, liver tissue and peripheral blood mononuclear cells (PBMCs) of patients with PBC. Results: Serum expressions of miR-21 and miR-150 were significantly enhanced in AMA-negative patients, and they inversely correlated with disease-specific AMA titers in PBS patients. In PBMCs, an increased expression of miR-21 correlated with decreased levels of RASGRP1 and DNMT1 mRNAs whereas, the level of miR-150 remained comparable to controls; and cMyb mRNA was downregulated. In cirrhotic livers, the level of miR-21 was unchanged while miR-150 expression was increased. Conclusion: This study convincingly report, that AMA-negative PBC is characterized by notable alternations of miR-21 and miR-150 and their downstream targets compared to AMA-positive patients underlining their possible importance in the induction of the disease and its progression to fibrosis.

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Section: Introductionmentioning

confidence: 99%

Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis

Wasik

Kempińska-Podhorodecka

Bogdanos

et al. 2020

Mol Med

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“…Bergman et al 19,20 The expression of this miRNA is also increased in serum and exosomes from activated lymphocytes and is therefore considered as a sensor for activation of adaptive immunity. 21 In this study, however, miR-150-5p was not upregulated in peripheral compartments, again suggesting the predominance of intrathecally mediated immune processes.…”

Section: Csf-predominant Mirna Dysregulation and Mirna Species Newly mentioning

confidence: 99%

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Perdaens

Dang

D’Auria

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo perform a comprehensive multicompartment analysis of microRNA (miRNA) expression in multiple sclerosis (MS) linked to disease activity and compared with other neuroinflammatory diseases through a retrospective cross-sectional study.MethodsOne hundred twenty-seven miRNAs were measured by PCR arrays on pooled CSF, serum, and peripheral blood mononuclear cell (PBMC) samples of 10 patients with relapsing MS and 10 controls. Sixty-four miRNAs were then measured by quantitative PCR on individual CSF samples of patients with relapsing or remitting MS and controls (n = 68). Fifty-seven miRNAs were analyzed in the CSF from a second cohort (n = 75), including patients with MS, neuroinfectious, or neuroinflammatory diseases and controls. MiRNAs significantly dysregulated in the CSF were analyzed on individual serum/PBMC samples (n = 59/48) of patients with relapsing or remitting MS and controls. Post hoc analysis consisted of principal component analysis (PCA), gene set, and pathway enrichment analysis.ResultsTwenty-one miRNAs were differentially expressed, mainly upregulated in the CSF during MS relapses. Relapsing MS and neuroinfectious/inflammatory diseases exhibited a partially overlapping CSF miRNA expression profile. Besides confirming the association of miR-146a-5p/150-5p/155-5p with MS, 7 miRNAs uncharacterized for MS emerged (miR-15a-3p/124-5p/149-3p/29c-3p/33a-3p/34c-5p/297). PCA showed that distinct miRNA sets segregated MS from controls and relapse from remission. In silico analysis predicted the involvement of these miRNAs in cell cycle, immunoregulation, and neurogenesis, but also revealed that the signaling pathway pattern of remitting MS is more akin to controls rather than patients with relapsing MS.ConclusionsThis study highlights the CSF-predominant dysregulation of miRNAs in MS by identifying a signature of disease activity and intrathecal inflammation among neuroinflammatory disorders.

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“…After excluding letters, reviews, and meta-analysis, three articles were added through retrospective research after reading the reference publications. Eleven articles were finally enrolled in this meta-analysis (16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Literature Search Processmentioning

confidence: 99%

A Meta-Analytic Review of the Value of miRNA for Multiple Sclerosis Diagnosis

et al. 2020

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Backgrounds and Purpose: Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. The etiology of MS is unclear, disease diagnosis mainly based on symptoms, and lacks effective laboratory test index. Circulating microRNAs (miRNAs) as sensitive biomarkers have been widely studied, the expression levels of certain miRNAs are dynamically changed in MS patients. This meta-analysis aims to assess the overall diagnostic accuracy of circulating miRNAs for MS. Methods: We searched PubMed, EMBASE, Cochrane Library, CNKI databases as of July 20, 2019. QUADAS was used to assess the quality of included studies. All studies were processed by Stata 15.0 software. Eleven articles with 600 patients with MS and 389 controls were included. Results: The sensitivity and specificity, PLR, NLR, and DOR of the overall studies were 0.81 (95% CI 0.77-0.84), 0.75 (95% CI 0.68-0.81), 3.3 (95% CI 2.5-4.3), 0.25 (95% CI 0.20-0.32), 13 (95% CI: 8-20), and 0.85 (95% CI 0.82-0.88). Subgroup analysis indicated that miRNA assay had higher diagnostic accuracy for relapsing-remitting MS (RRMS) when compared with other MS subtypes. Conclusion: Our study performed a meta-analysis to generate an estimate of the relevance of miRNA change and the occurrence of MS, and revealed circulating miRNAs has the potential to be used for MS diagnosis, especially for RRMS. Future studies should clarify to which specific miRNAs can accurately diagnose disease subtypes. The miRNA-related pathogenesis may provide theoretical basis for drug development for early intervention.

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Circulating miR-150 in CSF is a novel candidate biomarker for multiple sclerosis

Cited by 96 publications

References 40 publications

Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis

Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

A Meta-Analytic Review of the Value of miRNA for Multiple Sclerosis Diagnosis

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