Torres Iglesias, GabrielFernández-Fournier, MireyaBotella, LucíaPiniella, DoloresLaso-García, FernandoGómez-de Frutos, Mari CarmenChamorro, BeatrizPuertas, InmaculadaTallón Barranco, AntonioFuentes, BlancaAlonso de Leciñana, MariaAlonso-López, ElisaBravo, Susana-BelénMiranda-Carús, María EugeniaMontero-Calle, Ana MariaBarderas Manchado, RodrigoDíez-Tejedor, ExuperioGutiérrez-Fernández, MaríaOtero-Ortega, Laura2023-07-132023-07-132023Brain Behav Immun. 2023 Oct;113:44-55.http://hdl.handle.net/20.500.12105/16233Background: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes. Purpose: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. Results: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen β chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. Conclusion: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MS for reflecting the disease state.engVoRhttp://creativecommons.org/licenses/by/4.0/BiomarkersBloodExosomesExtracellular VesiclesMultiple SclerosisProteomic AnalysisRheumatoid ArthritisSubcortical StrokeAtribución 4.0 Internacional3740697611344-5510.1016/j.bbi.2023.06.0251090-2139Brain, behavior, and immunityopen access