Analysis of Plasma Using Flow Cytometry Reveals Increased Immune Cell-Derived Extracellular Vesicles in Untreated Relapsing-Remitting Multiple Sclerosis

Abstract

Extracellular vesicles (EVs) are secreted from cells under physiological and pathological conditions, and are found in biological fluids while displaying specific surface markers that are indicative of their cell of origin. EVs have emerged as important signaling entities that may serve as putative biomarkers for various neurological conditions, including multiple sclerosis (MS). The objective of this study was to measure and compare immune cell-derived EVs within human plasma between untreated RRMS patients and healthy controls. Using blood plasma and peripheral blood mononuclear cells (PBMCs) collected from RRMS patients and controls, PBMCs and EVs were stained and quantified by flow cytometry using antibodies against CD9, CD61, CD45, CD3, CD4, CD8, CD14, and CD19. While several immune cell-derived EVs, including CD3+, CD4+, CD8+, CD14+, and CD19+ were significantly increased in RRMS vs. controls, no differences in immune cell subsets were observed with the exception of increased circulating CD19+ cells in RRMS patients. Our study demonstrated that plasma-derived EVs secreted from T cells, B cells, and monocytes were elevated in untreated RRMS cases with low disability, despite very limited changes in circulating immune cells, and suggest the utility of circulating EVs as biomarkers in MS.