Abstract
Background:
Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication. An increase in plasma-borne EVs has been observed in Multiple Sclerosis (MS) and since EVs may cross the blood-brain barrier and elicit altered immune responses, EVs may present a link between peripheral inflammation and the
central nervous system.
Objective:
To determine if the cellular origin of plasma-borne EVs differs between MS subtypes and healthy controls (HCs).
Methods:
Platelet-free plasma was obtained from 13 relapsingremitting MS (RRMS), 8 secondary progressive MS (SPMS), and 17 matched HCs, stained with CD235a-APC (erythrocytederived), 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).
Results:
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 endotheliumderived 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, erythrocytederived, 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.
Conclusions: 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.
Disclosures:
Professor J. Lechner-Scott’s institution receives non-directed funding, as well as honoraria for presentations and membership on advisory boards from Sanofi Aventis, Biogen Idec, Bayer Health Care, Merck Serono, Teva, Roche, and
Novartis, Australia. Professor R. Scott has nothing to disclose.
Associate Professor L. Tajouri has nothing to disclose
Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication. An increase in plasma-borne EVs has been observed in Multiple Sclerosis (MS) and since EVs may cross the blood-brain barrier and elicit altered immune responses, EVs may present a link between peripheral inflammation and the
central nervous system.
Objective:
To determine if the cellular origin of plasma-borne EVs differs between MS subtypes and healthy controls (HCs).
Methods:
Platelet-free plasma was obtained from 13 relapsingremitting MS (RRMS), 8 secondary progressive MS (SPMS), and 17 matched HCs, stained with CD235a-APC (erythrocytederived), 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).
Results:
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 endotheliumderived 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, erythrocytederived, 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.
Conclusions: 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.
Disclosures:
Professor J. Lechner-Scott’s institution receives non-directed funding, as well as honoraria for presentations and membership on advisory boards from Sanofi Aventis, Biogen Idec, Bayer Health Care, Merck Serono, Teva, Roche, and
Novartis, Australia. Professor R. Scott has nothing to disclose.
Associate Professor L. Tajouri has nothing to disclose
| Original language | English |
|---|---|
| Article number | O-18 |
| Pages (from-to) | 443-444 |
| Number of pages | 2 |
| Journal | Multiple Sclerosis Journal |
| Volume | 25 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2019 |
| Event | Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) - Sydney, Australia Duration: 1 Nov 2018 → 3 Nov 2020 |