Exosomal microRNA signatures in multiple sclerosis reflect disease status.
Saeideh EbrahimkhaniFatemeh VafaeePaul E YoungSuzy S J HurSimon HawkeEmma DevenneyHeidi BeadnallMichael H BarnettCatherine M SuterMichael E BucklandPublished in: Scientific reports (2017)
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no single definitive test for MS. Circulating exosomes represent promising candidate biomarkers for a host of human diseases. Exosomes contain RNA, DNA, and proteins, can cross the blood-brain barrier, and are secreted from almost all cell types including cells of the CNS. We hypothesized that serum exosomal miRNAs could present a useful blood-based assay for MS disease detection and monitoring. Exosome-associated microRNAs in serum samples from MS patients (n = 25) and matched healthy controls (n = 11) were profiled using small RNA next generation sequencing. We identified differentially expressed exosomal miRNAs in both relapsing-remitting MS (RRMS) (miR-15b-5p, miR-451a, miR-30b-5p, miR-342-3p) and progressive MS patient sera (miR-127-3p, miR-370-3p, miR-409-3p, miR-432-5p) in relation to controls. Critically, we identified a group of nine miRNAs (miR-15b-5p, miR-23a-3p, miR-223-3p, miR-374a-5p, miR-30b-5p, miR-433-3p, miR-485-3p, miR-342-3p, miR-432-5p) that distinguished relapsing-remitting from progressive disease. Eight out of nine miRNAs were validated in an independent group (n = 11) of progressive MS cases. This is the first demonstration that microRNAs associated with circulating exosomes are informative biomarkers not only for the diagnosis of MS, but in predicting disease subtype with a high degree of accuracy.
Keyphrases
- multiple sclerosis
- white matter
- mesenchymal stem cells
- mass spectrometry
- stem cells
- end stage renal disease
- cell proliferation
- chronic kidney disease
- oxidative stress
- ejection fraction
- gene expression
- prognostic factors
- blood brain barrier
- newly diagnosed
- circulating tumor
- radiation therapy
- cell death
- bone marrow
- cerebrospinal fluid
- peritoneal dialysis
- signaling pathway
- induced pluripotent stem cells