Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers
IntroductionMultiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release aut...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1224217/full |
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| author | Gabriel Torres Iglesias Mireya Fernández-Fournier MariPaz López-Molina Dolores Piniella Fernando Laso-García Mari Carmen Gómez-de Frutos Elisa Alonso-López Lucía Botella Beatriz Chamorro Sara Sánchez-Velasco Inmaculada Puertas Antonio Tallón Barranco Pilar Nozal Exuperio Díez-Tejedor María Gutiérrez-Fernández Laura Otero-Ortega |
| author_facet | Gabriel Torres Iglesias Mireya Fernández-Fournier MariPaz López-Molina Dolores Piniella Fernando Laso-García Mari Carmen Gómez-de Frutos Elisa Alonso-López Lucía Botella Beatriz Chamorro Sara Sánchez-Velasco Inmaculada Puertas Antonio Tallón Barranco Pilar Nozal Exuperio Díez-Tejedor María Gutiérrez-Fernández Laura Otero-Ortega |
| author_sort | Gabriel Torres Iglesias |
| collection | DOAJ |
| description | IntroductionMultiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release autoreactive antibodies against myelin. The aim of the present study was to investigate whether extracellular vesicles (EVs) mediate delivery of myelin autoreactive antibodies from peripheral B cells against oligodendrocytes in multiple sclerosis (MS) and to analyze whether these EVs could mediate demyelination in vitro. We also studied the role of these EV-derived myelin antibodies as a diagnostic biomarker in MS.MethodsThis is a prospective, observational, and single-center study that includes patients with MS and two control groups: patients with non-immune white matter lesions and healthy controls. We isolated B-cell-derived EVs from the blood and cerebrospinal fluid (CSF) and analyzed their myelin antibody content. We also studied whether antibody-loaded EVs reach oligodendrocytes in patients with MS and the effect on demyelination of B-cell-derived EVs containing antibodies in vitro.ResultsThis study enrolled 136 MS patients, 23 white matter lesions controls, and 39 healthy controls. We found autoreactive myelin antibodies in EVs that were released by peripheral B cells, but not by populations of B cells resident in CSF. We also identified a cut-off of 3.95 ng/mL of myelin basic protein autoantibodies in EVs from peripheral B cells, with 95.2% sensitivity and 88.2% specificity, which allows us to differentiate MS patients from healthy controls. EV-derived myelin antibodies were also detected in the oligodendrocytes of MS patients. Myelin antibody-loaded EVs from B cells induced myelin markers decrease of oligodendrocytes in vitro.DiscussionPeripheral reactive immune cells could contribute remotely to MS pathogenesis by delivering myelin antibodies to oligodendrocytes. EV-derived myelin antibodies could play a role as diagnostic biomarker in MS. |
| first_indexed | 2024-03-12T15:23:18Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T15:23:18Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-f1f70c3ff4ab4f559b60de1af29695b02023-08-10T21:44:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12242171224217Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkersGabriel Torres Iglesias0Mireya Fernández-Fournier1MariPaz López-Molina2Dolores Piniella3Fernando Laso-García4Mari Carmen Gómez-de Frutos5Elisa Alonso-López6Lucía Botella7Beatriz Chamorro8Sara Sánchez-Velasco9Inmaculada Puertas10Antonio Tallón Barranco11Pilar Nozal12Exuperio Díez-Tejedor13María Gutiérrez-Fernández14Laura Otero-Ortega15Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainImmunology Department, La Paz University Hospital, IdiPAZ Health Research Institute, Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainNeurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Hospital Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, SpainIntroductionMultiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release autoreactive antibodies against myelin. The aim of the present study was to investigate whether extracellular vesicles (EVs) mediate delivery of myelin autoreactive antibodies from peripheral B cells against oligodendrocytes in multiple sclerosis (MS) and to analyze whether these EVs could mediate demyelination in vitro. We also studied the role of these EV-derived myelin antibodies as a diagnostic biomarker in MS.MethodsThis is a prospective, observational, and single-center study that includes patients with MS and two control groups: patients with non-immune white matter lesions and healthy controls. We isolated B-cell-derived EVs from the blood and cerebrospinal fluid (CSF) and analyzed their myelin antibody content. We also studied whether antibody-loaded EVs reach oligodendrocytes in patients with MS and the effect on demyelination of B-cell-derived EVs containing antibodies in vitro.ResultsThis study enrolled 136 MS patients, 23 white matter lesions controls, and 39 healthy controls. We found autoreactive myelin antibodies in EVs that were released by peripheral B cells, but not by populations of B cells resident in CSF. We also identified a cut-off of 3.95 ng/mL of myelin basic protein autoantibodies in EVs from peripheral B cells, with 95.2% sensitivity and 88.2% specificity, which allows us to differentiate MS patients from healthy controls. EV-derived myelin antibodies were also detected in the oligodendrocytes of MS patients. Myelin antibody-loaded EVs from B cells induced myelin markers decrease of oligodendrocytes in vitro.DiscussionPeripheral reactive immune cells could contribute remotely to MS pathogenesis by delivering myelin antibodies to oligodendrocytes. EV-derived myelin antibodies could play a role as diagnostic biomarker in MS.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1224217/fulldemyelinationserum diagnostic biomarkersextracellular vesiclesmultiple sclerosismyelin antibodies |
| spellingShingle | Gabriel Torres Iglesias Mireya Fernández-Fournier MariPaz López-Molina Dolores Piniella Fernando Laso-García Mari Carmen Gómez-de Frutos Elisa Alonso-López Lucía Botella Beatriz Chamorro Sara Sánchez-Velasco Inmaculada Puertas Antonio Tallón Barranco Pilar Nozal Exuperio Díez-Tejedor María Gutiérrez-Fernández Laura Otero-Ortega Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers Frontiers in Immunology demyelination serum diagnostic biomarkers extracellular vesicles multiple sclerosis myelin antibodies |
| title | Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers |
| title_full | Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers |
| title_fullStr | Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers |
| title_full_unstemmed | Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers |
| title_short | Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers |
| title_sort | dual role of peripheral b cells in multiple sclerosis emerging remote players in demyelination and novel diagnostic biomarkers |
| topic | demyelination serum diagnostic biomarkers extracellular vesicles multiple sclerosis myelin antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1224217/full |
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