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Abstract

Background:

MicroRNAs (miRNAs) are non-coding RNAs that regulate cellular processes by controlling protein translation and mRNA degradation.

Objective:

We aimed to explore the miRNA signature of multiple sclerosis (MS) patients versus controls and the possibility that patients with lipid-specific oligolconal IgM bands (LS_OCMB), a predictor of a more severe disease course, may have a distinct profile.

Methods:

An extensive profile of 754 miRNAs was evaluated in the cerebrospinal fluid (CSF) of 14 women using TaqMan low-density arrays. Differentially expressed miRNAs together with others previously identified in the literature were validated in an extended sample of 86 MS patients (39 LS_OCMB+) and 55 controls.

Results:

We detected higher levels of miR-150 in MS patients and especially in those with LS_OCMB+. Other miRNAs (miR-328, miR-30a-5p and miR-645) were up-regulated in MS patients compared to controls while miR-21, miR-199a-3p, miR-191, miR-365, miR-106a and miR-146a showed down-regulated expression. Considering only patients with LS_OCMB+, we also detected up-regulation of miR-30a-5p, miR-150 and miR-645 and down-regulation of miR-191 compared to controls.

Conclusion:

Our study confirms the recent findings regarding the deregulated expression of miR-150 not only with MS but also with the presence of LS_OCMB. This study highlights the potential utility of miRNAs in CSF as biomarkers for MS.

Keywords

MicroRNAs multiple sclerosis cerebrospinal fluid lipid-specific oligoclonal IgM bands biomarkers

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References

Noseworthy

Lucchinetti

Rodriguez

et al . Multiple sclerosis. N Engl J Med 2000; 343: 938–952.

Villar

Garcia-Barragan

Espino

et al . Influence of oligoclonal IgM specificity in multiple sclerosis disease course. Mult Scler 2008; 14: 183–187.

Thangarajh

Gomez-Rial

Hedstrom

et al . Lipid-specific immunoglobulin M in CSF predicts adverse long-term outcome in multiple sclerosis. Mult Scler 2008; 14: 1208–1213.

Magraner

Bosca

Simo-Castello

et al . Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes. Neuroradiology 2012; 54: 5–12.

Mendell

Olson

EN.

MicroRNAs in stress signaling and human disease. Cell 2012; 148: 1172–1187.

Gilad

Meiri

Yogev

et al . Serum microRNAs are promising novel biomarkers. PLoS ONE 2008; 3: e3148.

Cogswell

Ward

Taylor

et al . Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 2008; 14: 27–41.

Valadi

Ekstrom

Bossios

et al . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654–659.

Haghikia

Hellwig

Baraniskin

et al . Regulated microRNAs in the CSF of patients with multiple sclerosis: A case-control study. Neurology 2012; 79: 2166–2170.

10.

Ahlbrecht

Martino

Pul

et al . Deregulation of microRNA-181c in cerebrospinal fluid of patients with clinically isolated syndrome is associated with early conversion to relapsing-remitting multiple sclerosis. Mult Scler 2016; 22: 1202–1214.

11.

Bergman

Piket

Khademi

et al . Circulating miR-150 in CSF is a novel candidate biomarker for multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2016; 3: e219.

12.

Villar

Gonzalez-Porque

Masjuan

et al . A sensitive and reproducible method for the detection of oligoclonal IgM bands. J Immunol Methods 2001; 258: 151–155.

13.

Villar

Sadaba

Roldan

et al . Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest 2005; 115: 187–194.

14.

Ortega

Mercader

Catalan

et al . Targeting the circulating microRNA signature of obesity. Clin Chem 2013; 59: 781–792.

15.

Mestdagh

Van Vlierberghe

De Weer

et al . A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol 2009; 10: R64.

16.

Wylie

Shelton

Choudhary

et al . A novel mean-centering method for normalizing microRNA expression from high-throughput RT-qPCR data. BMC Res Notes 2011; 4: 555.

17.

Waschbisch

Atiya

Linker

et al . Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. PLoS ONE 2011; 6: e24604.

18.

Fenoglio

Cantoni

De Riz

et al . Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis. Neurosci Lett 2011; 504: 9–12.

19.

Junker

Krumbholz

Eisele

et al . MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 2009; 132: 3342–3352.

20.

Zampetaki

Willeit

Drozdov

et al . Profiling of circulating microRNAs: From single biomarkers to re-wired networks. Cardiovasc Res 2012; 93: 555–562.

21.

Shen

Stass

Jiang

MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett 2013; 329: 125–136.

22.

Murtaza

Dawson

Tsui

et al . Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108–112.

23.

Kosaka

Yoshioka

Hagiwara

et al . Trash or Treasure: extracellular microRNAs and cell-to-cell communication. Front Genet 2013; 4: 173.

24.

Otaegui

Baranzini

Armananzas

et al . Differential microRNA expression in PBMC from multiple sclerosis patients. PLoS ONE 2009; 4: e6309.

25.

Siegel

Mackenzie

Chaplin

et al . Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep 2012; 39: 6219–6225.

26.

Gandhi

miRNA in multiple sclerosis: search for novel biomarkers. Mult Scler 2015; 21: 1095–1103.

27.

Huang

Zhang

et al . MicroRNA-150: A potential regulator in pathogens infection and autoimmune diseases. Autoimmunity 2015; 48: 503–510.

28.

Spear

Boytard

Blervaque

et al . Adventitial tertiary lymphoid organs as potential source of MicroRNA biomarkers for abdominal aortic aneurysm. Int J Mol Sci 2015; 16: 11276–11293.

29.

Mellios

Huang

Grigorenko

A set of differentially expressed miRNAs, including miR-30a-5p, act as post-transcriptional inhibitors of BDNF in prefrontal cortex. Human Molec Genet 2008; 19: 3030–3042.

Supplementary Material

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miRNAs in cerebrospinal fluid identify patients with MS and specifically those with lipid-specific oligoclonal IgM bands

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material