Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16233
Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
Torres Iglesias, Gabriel | Fernández-Fournier, Mireya | Botella, Lucía | Piniella, Dolores | Laso-García, Fernando | Carmen Gómez-de Frutos, Mari | Chamorro, Beatriz | Puertas, Inmaculada | Tallón Barranco, Antonio | Fuentes, Blanca | Alonso de Leciñana, Maria | Alonso-López, Elisa | Bravo, Susana B | Eugenia Miranda-Carús, María | Montero-Calle, Ana Maria ISCIII | Barderas Manchado, Rodrigo ISCIII | Díez-Tejedor, Exuperio | Gutiérrez-Fernández, María | Otero-Ortega, Laura
Brain Behav Immun. 2023 Oct;113:44-55.
Background: 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.
Biomarkers | Blood | Exosomes | Extracellular Vesicles | Multiple Sclerosis | Proteomic Analysis | Rheumatoid Arthritis | Subcortical Stroke
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