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

• Published in: Neurology : neuroimmunology & neuroinflammation Vol. 3; no. 3; p. e219
• Main Authors: Bergman, Petra, Piket, Eliane, Khademi, Mohsen, James, Tojo, Brundin, Lou, Olsson, Tomas, Piehl, Fredrik, Jagodic, Maja
• Format: Journal Article
• Language: English
• Published: United States American Academy of Neurology 01.06.2016; Lippincott Williams & Wilkins
• Subjects: Medicin och hälsovetenskap
• ISSN: 2332-7812; 2332-7812
• DOI: 10.1212/NXI.0000000000000219

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.