Concentrations of plasma-borne extracellular particles differ between multiple sclerosis disease courses and compared to healthy controls.

ABSTRACT

BACKGROUND: Multiple sclerosis is a neurodegenerative, autoimmune disease of the central nervous system. Both peripheral blood and central nervous system facets play a role in the pathophysiology. Extracellular vesicles are small membrane-bound vesicles that are released by most cells in response to stress, activation, or pathology. As extracellular vesicles can cross the blood-brain barrier, they have the ability to link peripheral blood inflammation to central nervous system pathology in multiple sclerosis. The aim of this study was to obtain a comprehensive picture of the cellular origins of plasma-borne extracellular particles in multiple sclerosis. METHODS: Platelet-free plasma was obtained from 39 multiple sclerosis patients and 27 healthy controls via a series of centrifugation steps and assessed by flow cytometry. Plasma samples were stained with antibodies against CD4, CD8, CD14, CD20, CD41b, CD45, CD146, and CD235a. Gates were set using size-reference beads and extracellular particles were enumerated using commercial counting beads at known concentrations. RESULTS: In relapsing patients (n = 13) erythrocyte-derived (CD235a) extracellular particles were increased, while platelet-derived (CD41b), leukocyte-derived (CD45), and CD4+T cell-derived (CD4) extracellular particles were decreased compared to both healthy controls (n = 27) (p<0.05) and secondary progressive multiple sclerosis patients (n = 9) (p < 0.05). Endothelium-derived extracellular particles (CD146) were increased in stable relapsing-remitting multiple sclerosis patients (n = 17) compared to healthy controls (p < 0.05). Extracellular particles from several different cells of origin correlated with each other and clinical parameters (e.g. disease duration, number of relapses, EDSS), though clinical correlations did not withstand corrections for multiple comparisons. CONCLUSIONS: Concentrations of erythrocyte-, leukocyte-, and platelet-derived extracellular particles were altered in relapsing multiple sclerosis patients and endothelium-derived extracellular particles were increased in stable relapsing-remitting patients compared to healthy controls. Extracellular particles may provide insights into altered the crosstalk between peripheral blood cells in multiple sclerosis, which may lead to the discovery of novel therapeutic targets.