Oral Presentation Australasian Extracellular Vesicles Conference 2018

Increased plasma-borne extracellular vesicles in Multiple Sclerosis – Where did they come from? (#21)

Kira Groen 1 2 , Sean Burnard 2 3 , Vicki E Maltby 1 2 , Rodney J Scott 2 3 4 , Lotti Tajouri 5 , Jeannette Lechner-Scott 1 2 6
  1. School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia
  2. Centre for Brain and Mental Health, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  3. School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia
  4. Division of Molecular Genetics, Pathology North, John Hunter Hospital, New Lambton Heights, NSW, Australia
  5. Faculty of Health and Medicine, Bond University, Robina, QLD, Australia
  6. Department of Neurology, John Hunter Hospital, New Lambton Heights, NSW, Australia

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.