Candidate biomarker of multiple sclerosis found in extracellular vesicles isolated from plasma

Extracellular vesicles (EVs) are membrane nanovesicles of diverse sizes secreted by different cell types and are involved in intercellular communication. EVs shuttle proteins, nucleic acids, and lipids that reflect their cellular origin and could mediate their biological function in recipient cells. EVs circulate in biological fluids and are considered as potential biomarkers that could be used to analyze and characterize disease development, course and response to treatment. EVs exhibit specific distribution of glycolipids and membrane organization, but little is known about the biological significance of this distribution or how it could contribute to pathological conditions such as multiple sclerosis (MS).

Researchers from the University of Illinois at Chicago provide the first description of sulfatide composition in plasma-derived EVs by ultra-high-performance liquid chromatography tandem mass spectrometry. They found that EVs of different sizes showed C16:0 sulfatide but no detectable levels of C18:0, C24:0, or C24:1 sulfatide species. Small EVs isolated at 100,000 × g-enriched in exosomes-from plasma of patients with MS showed a significant increase of C16:0 sulfatide compared with healthy controls. Nanoparticle tracking analysis showed that the particle size distribution in MS plasma was significantly different compared with healthy controls. Characterization of small EVs isolated from MS plasma showed similar protein content and similar levels of exosomal markers (Alix, Rab-5B) and vesicular marker MHC class I (major histocompatibility complex class I) compared with healthy controls. These findings indicate that C16:0 sulfatide associated with small EVs is a candidate biomarker for MS that could potentially reflect pathological changes associated with this disease and/or the effects of its treatment.

Characterization of small EVs isolated from plasma of patients with MS and healthy controls

A: Representative micrographs of EM analysis of plasma-derived EVs isolated at 100,000 × g (small EVs) of healthy control and patient with MS. Both samples showed populations of EVs with different diameters (between 30 and 200 nm). Scale bar = 1 μm. B: Plasma-derived EVs isolated at 100,000 × g showed exosomal (Alix and Rab5B) and vesicular (MHC I) markers by immunoblotting. C: Representative Western blot images of two MS and two healthy control cases (5 μg protein per lane). Similar levels of these proteins were found in patients with MS (filled circles) compared with healthy controls (○). Data are presented as median and interquartile range. IFN, interferon-β; GA, glatiramer acetate; Nat, natalizumab; SPMS, secondary progressive MS.