Sulfatides in extracellular vesicles isolated from plasma of multiple sclerosis patients

Abstract

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). We provide the first description of sulfatide composition in plasma-derived EVs by ultra-high-performance liquid chromatography tandem mass spectrometry. We 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. Our 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. © 2016 Wiley Periodicals, Inc.

Proteomic analysis of plasma extracellular vesicles reveals mitochondrial stress upon HTLV-1 infection

“…Such enrichment has not been previously reported, neither on samples from HIV-infected patients 17 nor in the context of inflammatory diseases (e.g. inflammatory bowel disease, multiple sclerosis) 11 , 18 . Of note, Dutta et al .…”

“…Changes in the size of an EV population are not uncommon. Smaller EVs have been previously observed in the context of inflammation, cellular stress and tissue damage 10 , 11 . These smaller vesicles could be either secreted by a particular cell type (that remains to be identified) or correspond to a change in secretion pattern by cells that otherwise secrete larger vesicles.…”

Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles

“…Another recent work revealed that a distinct SL (C16:0 sulfatide), a sulfated galactosylceramide with long-chain fatty acid, in blood EVs represents a unique indicator of multiple sclerosis, a chronic neuroinflammatory disease (116). Specifically, using ultra-high-performance LC tandem MS, Moyano et al (116) detected a significant increase in C16:0 sulfatide in EVs isolated from multiple sclerosis patients when compared with healthy subjects.…”

Glycan Node Analysis of Plasma-Derived Extracellular Vesicles

“…Additionally, studies have shown that certain plasma glycans (beyond N-linked glycans) are elevated in cancer patients when compared to healthy controls [ 29 , 30 , 31 , 32 ]. However, outside of a few studies targeting specific EV glycoproteins/proteoglycans or glycolipids [ 33 , 34 , 35 ], only a single study has assessed glycan expression levels in plasma based on association with EVs, and this analysis was limited to N-linked glycosylation [ 36 ]. The present study represents the first broad analysis of glycan expression (multiple glycan classes) in plasma-derived EVs.…”