Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis

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 membran...

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Autores: Torres Iglesias, G., Fernández-Fournier, M., Botella, L., Piniella, D., Laso-García, F., Carmen Gómez-de Frutos, M., Chamorro, B., Puertas, I., Tallón Barranco, A., Fuentes, B., Alonso de Leciñana, M., Alonso-López, E., Bravo López, Susana Belén, Eugenia Miranda-Carús, M., Montero-Calle, A., Barderas, R., Díez-Tejedor, E., Gutiérrez-Fernández, M., Otero-Ortega, L.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21165
Acceso en línea:https://portalcientifico.sergas.gal//documentos/64be32f43bbfc602eae5916c
http://hdl.handle.net/20.500.11940/21165
Access Level:acceso abierto
Palabra clave:Humans
Multiple Sclerosis
Proteomics
Brain
Extracellular Vesicles
Immune System
Extracellular Matrix
Biomarkers
AS Santiago
IDIS
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spelling Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosisTorres Iglesias, G.Fernández-Fournier, M.Botella, L.Piniella, D.Laso-García, F.Carmen Gómez-de Frutos, M.Chamorro, B.Puertas, I.Tallón Barranco, A.Fuentes, B.Alonso de Leciñana, M.Alonso-López, E.Bravo López, Susana BelénEugenia Miranda-Carús, M.Montero-Calle, A.Barderas, R.Díez-Tejedor, E.Gutiérrez-Fernández, M.Otero-Ortega, L.HumansMultiple SclerosisProteomicsBrainExtracellular VesiclesImmune SystemExtracellular MatrixBiomarkersAS SantiagoIDISBackground: 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 ? 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.We greatly appreciate the support of Morote Traducciones S.L. for their editing assistance. This work was sponsored by a grant from Miguel Servet (CP20/00024 to Laura Otero-Ortega) , Miguel Servet (CPII20/00002 to Maria Gutie'rrez-Fern'andez) , a predoctoral fellowship (FI18/00026 to Fernando Laso-Garcia) , a Rio-Hortega grant (CM22/00065 to Gabriel Torres Iglesias and CM20/00047 to Elisa Alonso-L'opez) and by Research Project (PI21/00918) from the Instituto de Salud Carlos III and co-funded by the European Union and by a grant CA1/RSUE/2021-00753 to Dolores Piniella funded by Ministerio de Universidades, Plan de Recuperaci'on, Transformaci'on y Resiliencia y la Universidad Aut'onoma de Madrid.2023info:eu-repo/semantics/articlehttps://portalcientifico.sergas.gal//documentos/64be32f43bbfc602eae5916chttp://hdl.handle.net/20.500.11940/21165reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/211652026-06-12T08:40:47Z
dc.title.none.fl_str_mv Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
title Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
spellingShingle 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, G.
Humans
Multiple Sclerosis
Proteomics
Brain
Extracellular Vesicles
Immune System
Extracellular Matrix
Biomarkers
AS Santiago
IDIS
title_short Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
title_full Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
title_fullStr Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
title_full_unstemmed Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
title_sort Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
dc.creator.none.fl_str_mv Torres Iglesias, G.
Fernández-Fournier, M.
Botella, L.
Piniella, D.
Laso-García, F.
Carmen Gómez-de Frutos, M.
Chamorro, B.
Puertas, I.
Tallón Barranco, A.
Fuentes, B.
Alonso de Leciñana, M.
Alonso-López, E.
Bravo López, Susana Belén
Eugenia Miranda-Carús, M.
Montero-Calle, A.
Barderas, R.
Díez-Tejedor, E.
Gutiérrez-Fernández, M.
Otero-Ortega, L.
author Torres Iglesias, G.
author_facet Torres Iglesias, G.
Fernández-Fournier, M.
Botella, L.
Piniella, D.
Laso-García, F.
Carmen Gómez-de Frutos, M.
Chamorro, B.
Puertas, I.
Tallón Barranco, A.
Fuentes, B.
Alonso de Leciñana, M.
Alonso-López, E.
Bravo López, Susana Belén
Eugenia Miranda-Carús, M.
Montero-Calle, A.
Barderas, R.
Díez-Tejedor, E.
Gutiérrez-Fernández, M.
Otero-Ortega, L.
author_role author
author2 Fernández-Fournier, M.
Botella, L.
Piniella, D.
Laso-García, F.
Carmen Gómez-de Frutos, M.
Chamorro, B.
Puertas, I.
Tallón Barranco, A.
Fuentes, B.
Alonso de Leciñana, M.
Alonso-López, E.
Bravo López, Susana Belén
Eugenia Miranda-Carús, M.
Montero-Calle, A.
Barderas, R.
Díez-Tejedor, E.
Gutiérrez-Fernández, M.
Otero-Ortega, L.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Humans
Multiple Sclerosis
Proteomics
Brain
Extracellular Vesicles
Immune System
Extracellular Matrix
Biomarkers
AS Santiago
IDIS
topic Humans
Multiple Sclerosis
Proteomics
Brain
Extracellular Vesicles
Immune System
Extracellular Matrix
Biomarkers
AS Santiago
IDIS
description 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 ? 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://portalcientifico.sergas.gal//documentos/64be32f43bbfc602eae5916c
http://hdl.handle.net/20.500.11940/21165
url https://portalcientifico.sergas.gal//documentos/64be32f43bbfc602eae5916c
http://hdl.handle.net/20.500.11940/21165
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
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