BACKGROUND: Exosomes are small extracellular vesicles that provide cell-to-cell communication and are involved in immunoregulation. OBJECTIVE: To investigate serum exosomes for the presence of myelin proteins outside the central nervous system (CNS) and their role in multiple sclerosis (MS). METHODS: Serum, cerebrospinal fluid (CSF), and peripheral blood mononuclear cell (PBMC) samples were collected from 45 patients with relapsing-remitting MS (RRMS), 30 patients with secondary progressive MS (SPMS), and 45 healthy controls. Exosomes were isolated using a polymer formulation method, and their size, concentration, and CNS myelin protein contents were measured by a nanoparticle tracking analysis, enzyme-linked immunosorbent assays, and Western blot. RESULTS: We found that exosomes expressed three major myelin proteins, myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG). Exosomal content of MOG strongly correlated with disease activity and was highest in RRMS patients in relapse and in SPMS patients. Serum-derived exosomes induced proliferation of MOG-T cell receptor transgenic T cells confirming that serum exosomes maintained MOG immunogenicity. CONCLUSION: Exosomes isolated outside CNS tissue expressed myelin proteins, and the presence of MOG correlated strongly with disease activity. We conclude that exosomes might enhance and/or perpetuate anti-myelin immune reactions in MS and may provide novel markers of disease activity.
BACKGROUND: Exosomes are small extracellular vesicles that provide cell-to-cell communication and are involved in immunoregulation. OBJECTIVE: To investigate serum exosomes for the presence of myelin proteins outside the central nervous system (CNS) and their role in multiple sclerosis (MS). METHODS: Serum, cerebrospinal fluid (CSF), and peripheral blood mononuclear cell (PBMC) samples were collected from 45 patients with relapsing-remitting MS (RRMS), 30 patients with secondary progressive MS (SPMS), and 45 healthy controls. Exosomes were isolated using a polymer formulation method, and their size, concentration, and CNS myelin protein contents were measured by a nanoparticle tracking analysis, enzyme-linked immunosorbent assays, and Western blot. RESULTS: We found that exosomes expressed three major myelin proteins, myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG). Exosomal content of MOG strongly correlated with disease activity and was highest in RRMS patients in relapse and in SPMS patients. Serum-derived exosomes induced proliferation of MOG-T cell receptor transgenic T cells confirming that serum exosomes maintained MOG immunogenicity. CONCLUSION: Exosomes isolated outside CNS tissue expressed myelin proteins, and the presence of MOG correlated strongly with disease activity. We conclude that exosomes might enhance and/or perpetuate anti-myelin immune reactions in MS and may provide novel markers of disease activity.
Authors: Anudeep Yekula; Koushik Muralidharan; Keiko M Kang; Lan Wang; Leonora Balaj; Bob S Carter Journal: Methods Date: 2020-02-12 Impact factor: 3.608
Authors: Damiana Pieragostino; Ilaria Cicalini; Paola Lanuti; Eva Ercolino; Maria di Ioia; Mirco Zucchelli; Romina Zappacosta; Sebastiano Miscia; Marco Marchisio; Paolo Sacchetta; Marco Onofrj; Piero Del Boccio Journal: Sci Rep Date: 2018-02-15 Impact factor: 4.379
Authors: Ruturaj Masvekar; Jordan Mizrahi; John Park; Peter R Williamson; Bibiana Bielekova Journal: Front Neurol Date: 2019-11-26 Impact factor: 4.003