Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis

Keren Regev, Anu Paul, Brian Healy, Felipe von Glenn, Camilo Diaz-Cruz, Taha Gholipour, Maria Antonietta Mazzola, Radhika Raheja, Parham Nejad, Bonnie I. Glanz, Pia Kivisakk, Tanuja Chitnis, Howard L. Weiner, Roopali Gandhi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To identify circulating microRNAs (miRNAs) linked to disease stage and disability in multiple sclerosis (MS). Methods: Sera from 296 participants including patients with MS, other neurologic diseases (Alzheimer disease and amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis and asthma) and healthy controls (HCs) were tested. miRNA profiles were determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with MS were categorized according to disease stage and disability. In the discovery phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs. Following this, significant miRNAs (p, 0.05) from the discovery set were validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74 samples from other disease controls (Alzheimer disease, amyotrophic lateral sclerosis, asthma, and rheumatoid arthritis). Results: We validated 7 miRNAs that differentiate patients with MS from HCs (p, 0.05 in both the discovery and validation phase); miR-320a upregulation was the most significantly changing serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease progression, with miR-27a-3p being the most significant. Ten miRNAs correlated with the Expanded Disability Status Scale of which miR.199a.5p had the strongest correlation with disability. Of the 15 unique miRNAs we identified in the different group comparisons, 12 have previously been reported to be associated with MS but not in serum.

Original languageEnglish
Article numbere267
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume3
Issue number5
DOIs
StatePublished - 1 Oct 2016
Externally publishedYes

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