Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis

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.Conclusions:Our findings identify circulating serum miRNAs as potential biomarkers to diagnose and monitor disease status in MS.Classification of evidence:This study provides Class III evidence that circulating serum miRNAs can be used as biomarker for MS.

Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis

“…This is the first report using a global approach for the investigation of the circulating exosomes in RRMS. To date analysis of circulating serum miRNAs in MS has measured levels of free‐floating circulating miRNAs . Exosomal miRNA analysis provides a more robust and different dataset than an analysis of circulating serum small RNAs .…”

“…To date analysis of circulating serum miRNAs in MS has measured levels of free-floating circulating miRNAs. [18][19][20] Exosomal miRNA analysis provides a more robust and different dataset than an analysis of circulating serum small RNAs. 12 In this regard, data on exosomal miRNAs provide Zinc finger transcription factor, DNA-binding protein information on the spread of genetic messages and intercellular communication mediated by miRNAs.…”

Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

“…MicroRNAs have been proposed as biomarkers relevant to diagnosis, stage of disease, and response to treatment in MS. 33–35,53 Magnetic resonance imaging techniques have long contributed to the diagnosis and monitoring of the disease. 3 Imaging advances have allowed measurement of heterogeneous pathologic processes, allowing clustering of patients based on these differences.…”

Correlating serum micrornas and clinical parameters in amyotrophic lateral sclerosis

“…includes the detailed information about ALS diagnosis, treatment regimen, and the number of visits for each patient. Healthy controls (HC; 30 participants, 9 men and 21 women, average age 43 6 12.2 years) were recruited from the Brigham PhenoGenetic cohort study and from healthy participants enrolled in the Comprehensive Longi-Detailed characteristics of patients with ALS ALS, amyotrophic lateral sclerosis.of age, and had no chronic inflammatory, infectious, or metabolic diseases 24,25. Multiple sclerosis (MS) patient samples were obtained from the CLIMB study and included samples from patients with relapsing-remitting MS (29 patients, 12 men and 17 women, average age 36 6 8.0 years), secondary progressive MS (26 patients, 6 men and…”