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Mult Scler. 2016 Aug;22(9):1202-14. doi: 10.1177/1352458515613641. Epub 2015 Oct 22.

Deregulation of microRNA-181c in cerebrospinal fluid of patients with clinically isolated syndrome is associated with early conversion to relapsing-remitting multiple sclerosis.

Author information

1
Department of Neurology, Hannover Medical School, Germany.
2
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
3
Department of Neurology, University of Ulm, Germany.
4
Department of Neurology, University of Rostock, Germany.
5
Department of Neurology, Hannover Medical School, Germany stangel.martin@mhhannover.de.

Abstract

BACKGROUND:

MiRNA-181c, miRNA-633 and miRNA-922 have been reported to be deregulated in multiple sclerosis.

OBJECTIVES:

To investigate the association between miRNA-181c, miRNA-633 and miRNA-922 and conversion from clinically isolated syndrome (CIS) to relapsing-remitting multiple sclerosis (RRMS); and to compare microRNAs in cerebrospinal fluid (CSF) and serum with regard to dysfunction of the blood-CSF barrier.

METHODS:

CSF and serum miRNA-181c, miRNA-633 and miRNA-922 were retrospectively determined by quantitative real-time polymerase chain reaction in CIS patients with (CIS-RRMS) and without (CIS-CIS) conversion to RRMS within 1 year.

RESULTS:

Thirty of 58 CIS patients developed RRMS. Cerebrospinal fluid miRNA-922, serum miRNA-922 and cerebrospinal fluid miRNA-181c were significantly higher in CIS-RRMS compared to CIS-CIS (P=0.027, P=0.048, P=0.029, respectively). High levels of cerebrospinal fluid miRNA-181c were independently associated with conversion from CIS to RRMS in multivariate Cox regression analysis (hazard ratio 2.99, 95% confidence interval 1.41-6.34, P=0.005). A combination of high cerebrospinal fluid miRNA-181c, younger age and more than nine lesions on magnetic resonance imaging showed the highest specificity (96%) and positive predictive value (94%) for conversion from CIS to RRMS. MiRNA-181c was higher in serum than in cerebrospinal fluid (P <0.001), while miRNA-633 and miRNA-922 were no different in cerebrospinal fluid and serum. Cerebrospinal fluid/serum albumin quotients did not correlate with microRNAs in cerebrospinal fluid (all P>0.711).

CONCLUSIONS:

Cerebrospinal fluid miRNA-181c might serve as a biomarker for early conversion to RRMS. Moreover, our data suggest an intrathecal origin of microRNAs detected in the cerebrospinal fluid.

KEYWORDS:

MicroRNA; blood–cerebrospinal fluid barrier; cerebrospinal fluid; clinically isolated syndrome; conversion; multiple sclerosis

PMID:
26493127
DOI:
10.1177/1352458515613641
[Indexed for MEDLINE]

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