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Exosomal microRNA signatures in multiple sclerosis reflect disease status

Saeideh EbrahimkhaniBrain and Mind Centre, University of Sydney, Camperdown, NSW, AustraliaFatemeh VafaeeCharles Perkins Centre, University of Sydney, Camperdown, NSW, AustraliaPaul YoungDivision of Molecular Structural and Computational Biology, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, AustraliaSuzy S. J. HurDivision of Molecular Structural and Computational Biology, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, AustraliaSimon HawkeSydney Medical School, University of Sydney, Camperdown, NSW, AustraliaEmma DevenneyBrain and Mind Centre, University of Sydney, Camperdown, NSW, AustraliaHeidi BeadnallBrain and Mind Centre, University of Sydney, Camperdown, NSW, AustraliaMichael BarnettBrain and Mind Centre, University of Sydney, Camperdown, NSW, AustraliaCatherine M. SuterDivision of Molecular Structural and Computational Biology, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, AustraliaMichael E. BucklandBrain and Mind Centre, University of Sydney, Camperdown, NSW, Australia. [email protected]

2017en

ABI

Annotatsiya

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.

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DOI: 10.1038/s41598-017-14301-3

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