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


ABSTRACT:

Objective

To explore circulating microRNAs (miRNAs) in cell-free CSF as novel biomarkers for multiple sclerosis (MS).

Methods

Profiling of miRNAs in CSF of pooled patients with clinically isolated syndrome (CIS), patients with relapsing-remitting MS, and inflammatory and noninflammatory neurologic disease controls was performed using TaqMan miRNA arrays. Two independent patient cohorts (n = 142 and n = 430) were used for validation with real-time PCR.

Results

We reliably detected 88 CSF miRNAs in the exploratory cohort. Subsequent validation in 2 cohorts demonstrated significantly higher levels of miR-150 in patients with MS. Higher miR-150 levels were also observed in patients with CIS who converted to MS compared to nonconverters, and in patients initiating natalizumab treatment. Levels of miR-150 correlated with immunologic parameters including CSF cell count, immunoglobulin G index, and presence of oligoclonal bands, and with candidate protein biomarkers C-X-C motif chemokine 13, matrix metallopeptidase 9, and osteopontin. Correlation with neurofilament light chain (NFL) was observed only when NFL was adjusted for age using a method that requires further validation. Additionally, miR-150 discriminated MS from controls and CIS converters from nonconverters equally well as the most informative protein biomarkers. Following treatment with natalizumab, but not fingolimod, CSF levels of miR-150 decreased, while plasma levels increased with natalizumab and decreased with fingolimod, suggesting immune cells as a source of miR-150.

Conclusions

Our findings demonstrate miR-150 as a putative novel biomarker of inflammatory active disease with the potential to be used for early diagnosis of MS.

Classification of evidence

This study provides Class II evidence that CSF miR-150 distinguishes patients with MS from patients with other neurologic conditions.

SUBMITTER: Bergman P 

PROVIDER: S-EPMC4841644 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Bergman Petra P   Piket Eliane E   Khademi Mohsen M   James Tojo T   Brundin Lou L   Olsson Tomas T   Piehl Fredrik F   Jagodic Maja M  

Neurology(R) neuroimmunology & neuroinflammation 20160420 3


<h4>Objective</h4>To explore circulating microRNAs (miRNAs) in cell-free CSF as novel biomarkers for multiple sclerosis (MS).<h4>Methods</h4>Profiling of miRNAs in CSF of pooled patients with clinically isolated syndrome (CIS), patients with relapsing-remitting MS, and inflammatory and noninflammatory neurologic disease controls was performed using TaqMan miRNA arrays. Two independent patient cohorts (n = 142 and n = 430) were used for validation with real-time PCR.<h4>Results</h4>We reliably de  ...[more]

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