Multiple Sclerosis (MS) is an autoimmune disease in which lymphocytic infiltration of the central nervous system causes neurodegeneration. Most patients are diagnosed with more inflammatory relapsing-remitting MS (RRMS), and may progress to more neurodegenerative secondary progressive MS (SPMS). An increase in plasma-borne extracellular vesicles (EVs) has been observed in MS. The aim of this study was to determine the cellular origin of plasma-borne EVs in MS patients and healthy controls (HCs).
Platelet-free plasma was obtained from 13 relapsing-remitting MS (RRMS), 8 secondary progressive MS (SPMS), and 17 matched HCs, stained with CD235a-APC (erythrocyte-derived), CD41b-FITC (platelet-derived), CD45-FITC (leukocyte-derived), and CD146-PE (endothelium-derived) antibodies, and analysed on a LSR Fortessa (BD Biosciences). EV gates were set using size reference beads and quantified using CountBright Beads (Invitrogen).
RRMS patients’ endothelium-derived EVs positively correlated with number of relapses (P=0.02415, R=0.619). All EV subpopulations appeared increased in MS, with endothelium-derived EVs being the most abundant (3796±8355 EVs/µl, 3.66-fold, p=0.137), followed by erythrocyte-derived (2704±3729 EVs/µl, 2.65-fold, p=0.064), platelet-derived (2279±1337 EVs/µl, 1.09-fold, ns), and leukocyte-derived EVs (1900±2528 EVs/µl, 2.37-fold, p=0.071). In contrast, platelet-derived EVs were most prevalent in HCs, followed by endothelium-derived, erythrocyte-derived, and leukocyte-derived EVs. Comparing MS subtypes to HCs, erythrocyte-derived (3.08-fold) and endothelium-derived EVs (2.58-fold) showed greatest increases in RRMS, while endothelium-derived (6.87-fold) and leukocyte-derived EVs (3.51-fold) showed greatest increases in SPMS.
This preliminary data suggests there may be an increase in plasma-borne EVs in MS and monitoring of EV subpopulations may reflect underlying disease processes. Further, increases in EV subpopulations might differ between disease courses.