Contributions
Abstract: P1791
Type: Poster Sessions
Abstract Category: N/A
Advancements in technology have enabled the study of extracellular vesicles (EVs), which play a crucial role in cell-to-cell communication. Close interaction between endothelial cells and leukocytes is critical in the development of multiple sclerosis (MS) and lymphocytic infiltration of the central nervous system (CNS). An increase in plasma-borne EVs has been observed in MS and since EVs have the potential to cross the blood-brain barrier (BBB) and elicit altered immune responses, EVs may be a link between peripheral inflammation and the CNS. The aim of this study was to determine if the cellular origin of plasma-borne EVs in MS patients differ between subtypes and healthy controls (HCs).
Platelet-free plasma was obtained from 13 relapse-remitting multiple sclerosis (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).
A positive correlation for RRMS endothelium-derived EVs (/µl) and number of relapses was observed (P=0.02415, R= 0.619). This may be the result of greater BBB damage, which could release more endothelial EVs. All EV subpopulations appeared increased in MS, with endothelium-derived EVs being the most abundant (3796±8355 EVs/µl, 3.66-fold increase, p=0.137), followed by erythrocyte-derived (2704±3729 EVs/µl, 2.65-fold increase, p=0.064), platelet-derived (2279±1337 EVs/µl, 1.09-fold increase, ns), and leukocyte-derived EVs (1900±2528 EVs/µl, 2.37-fold increase, p=0.071). In HCs platelet-derived EVs were most prevalent (2085±1282 EVs/µl), followed by endothelium-derived (1036±491 EVs/µl), erythrocyte-derived (1021±758 EVs/µl), and leukocyte-derived EVs (803±414 EVs/µl). When comparing MS subtype to HCs, erythrocyte-derived (3.08-fold) and endothelium-derived EVs (2.58-fold) appear to show greatest increases in RRMS, while endothelium-derived (6.87-fold) and leukocyte-derived EVs (3.51-fold) appear to show greatest increases in SPMS.
This preliminary data suggests that 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. Recruitment is still ongoing to confirm these findings.
Disclosure: 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.
Funding: This project was funded by MS Research Australia (Incubator Grant). K. Groen is funded by a scholarship from the University of Newcastle. S. Burnard is funded by a scholarship from the University of Newcastle. Dr V.E. Maltby is funded by fellowships form Multiple Sclerosis Research Australia and the Canadian Institutes of Health Services.
Abstract: P1791
Type: Poster Sessions
Abstract Category: N/A
Advancements in technology have enabled the study of extracellular vesicles (EVs), which play a crucial role in cell-to-cell communication. Close interaction between endothelial cells and leukocytes is critical in the development of multiple sclerosis (MS) and lymphocytic infiltration of the central nervous system (CNS). An increase in plasma-borne EVs has been observed in MS and since EVs have the potential to cross the blood-brain barrier (BBB) and elicit altered immune responses, EVs may be a link between peripheral inflammation and the CNS. The aim of this study was to determine if the cellular origin of plasma-borne EVs in MS patients differ between subtypes and healthy controls (HCs).
Platelet-free plasma was obtained from 13 relapse-remitting multiple sclerosis (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).
A positive correlation for RRMS endothelium-derived EVs (/µl) and number of relapses was observed (P=0.02415, R= 0.619). This may be the result of greater BBB damage, which could release more endothelial EVs. All EV subpopulations appeared increased in MS, with endothelium-derived EVs being the most abundant (3796±8355 EVs/µl, 3.66-fold increase, p=0.137), followed by erythrocyte-derived (2704±3729 EVs/µl, 2.65-fold increase, p=0.064), platelet-derived (2279±1337 EVs/µl, 1.09-fold increase, ns), and leukocyte-derived EVs (1900±2528 EVs/µl, 2.37-fold increase, p=0.071). In HCs platelet-derived EVs were most prevalent (2085±1282 EVs/µl), followed by endothelium-derived (1036±491 EVs/µl), erythrocyte-derived (1021±758 EVs/µl), and leukocyte-derived EVs (803±414 EVs/µl). When comparing MS subtype to HCs, erythrocyte-derived (3.08-fold) and endothelium-derived EVs (2.58-fold) appear to show greatest increases in RRMS, while endothelium-derived (6.87-fold) and leukocyte-derived EVs (3.51-fold) appear to show greatest increases in SPMS.
This preliminary data suggests that 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. Recruitment is still ongoing to confirm these findings.
Disclosure: 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.
Funding: This project was funded by MS Research Australia (Incubator Grant). K. Groen is funded by a scholarship from the University of Newcastle. S. Burnard is funded by a scholarship from the University of Newcastle. Dr V.E. Maltby is funded by fellowships form Multiple Sclerosis Research Australia and the Canadian Institutes of Health Services.