Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis
BackgroundSerum biomarkers as neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enabled early identification of multiple sclerosis (MS) patients at risk of relapse-associated worsening (RAW) or progression independent of relapses (PIRA). However, the immunological mechanis...
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Frontiers Media S.A.
2025-08-01
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| author | Alexander Rodero-Romero José Ignacio Fernández-Velasco Enric Monreal Raquel Sainz-Amo Roberto Álvarez-Lafuente Manuel Comabella Manuel Comabella Lluís Ramió-Torrentà Lluís Ramió-Torrentà Lluís Ramió-Torrentà José M. García-Domínguez Noelia Villarrubia Susana Sainz de la Maza María Domínguez-Mozo Ana Quiroga-Varela Juan Luís Chico-García Fernando Rodriguez-Jorge José Luis Veiga-Gonzalez Ernesto Roldán-Santiago Mercedes Espiño Eulalia Rodríguez-Martín Gary Álvarez Jaime Masjuan Xavier Montalban Xavier Montalban Lucienne Costa-Frossard Luisa María Villar |
| author_facet | Alexander Rodero-Romero José Ignacio Fernández-Velasco Enric Monreal Raquel Sainz-Amo Roberto Álvarez-Lafuente Manuel Comabella Manuel Comabella Lluís Ramió-Torrentà Lluís Ramió-Torrentà Lluís Ramió-Torrentà José M. García-Domínguez Noelia Villarrubia Susana Sainz de la Maza María Domínguez-Mozo Ana Quiroga-Varela Juan Luís Chico-García Fernando Rodriguez-Jorge José Luis Veiga-Gonzalez Ernesto Roldán-Santiago Mercedes Espiño Eulalia Rodríguez-Martín Gary Álvarez Jaime Masjuan Xavier Montalban Xavier Montalban Lucienne Costa-Frossard Luisa María Villar |
| author_sort | Alexander Rodero-Romero |
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| description | BackgroundSerum biomarkers as neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enabled early identification of multiple sclerosis (MS) patients at risk of relapse-associated worsening (RAW) or progression independent of relapses (PIRA). However, the immunological mechanisms underlying these clinical phenotypes remain unclear.MethodsWe conducted a cross-sectional study including 117 MS patients and 84 healthy controls (HC). Patients were stratified as NLGL (low sNfL and sGFAP), NH (high sNfL at different levels of sGFAP), and NLGH (low sNfL and high sGFAP). Percentages of blood and cerebrospinal fluid (CSF) mononuclear cells, and intracellular production of cytokines by T and B cells after “in vitro” stimulation were analyzed by flow cytometry.ResultsWe identified a common inflammatory profile present in the blood of all MS groups comprising significant increases of effector CD4+ and CD8+ T cells, of memory and antigen-presenting B cells, of CD4+ and CD8+ T cells producing interferon-gamma, interleukin-17 and tumor necrosis factor-alpha (TNF-α) and of B cells producing TNF-α. Additionally, the highly inflammatory NH group showed lower frequencies of different regulatory subsets (transitional B cells, PDL1+ monocytes and Treg cells) compared to HC and increased percentages of CD4+ and CD8+ T cells producing granulocyte-macrophage colony-stimulating factor and of effector CD56dim NK cells. They also showed lower percentages of Treg in blood and CSF compared to the low inflammatory NLGL group, which also displayed higher frequencies of regulatory CD56dim, NKG2A+ cells.ConclusionAll MS patients share increased inflammatory B and T cells, but differ in regulatory or NK subsets, which identify highly inflammatory or benign disease courses. |
| format | Article |
| id | doaj-art-cbad4fc20695435ab4d8bdfecf041251 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-cbad4fc20695435ab4d8bdfecf0412512025-08-20T03:40:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16487251648725Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosisAlexander Rodero-Romero0José Ignacio Fernández-Velasco1Enric Monreal2Raquel Sainz-Amo3Roberto Álvarez-Lafuente4Manuel Comabella5Manuel Comabella6Lluís Ramió-Torrentà7Lluís Ramió-Torrentà8Lluís Ramió-Torrentà9José M. García-Domínguez10Noelia Villarrubia11Susana Sainz de la Maza12María Domínguez-Mozo13Ana Quiroga-Varela14Juan Luís Chico-García15Fernando Rodriguez-Jorge16José Luis Veiga-Gonzalez17Ernesto Roldán-Santiago18Mercedes Espiño19Eulalia Rodríguez-Martín20Gary Álvarez21Jaime Masjuan22Xavier Montalban23Xavier Montalban24Lucienne Costa-Frossard25Luisa María Villar26Department of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainGrupo Investigación de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, SpainServei de Neurologia, Centre d’Esclerosi Múltiple de Catalunya, Institut de Recerca Vall d’Hebron, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainCenter for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII, Madrid, SpainNeurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Salt, SpainRed de Enfermedades inflamatorias (RD24/0007/0005), Instituto de Salud Carlos III, Madrid, SpainMedical Sciences Department, Faculty of Medicine, Universitat de Girona, Girona, SpainDepartment of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainGrupo Investigación de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, SpainNeurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Salt, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainNeurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Salt, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainServei de Neurologia, Centre d’Esclerosi Múltiple de Catalunya, Institut de Recerca Vall d’Hebron, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainCenter for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII, Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), ISCIII, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, SpainBackgroundSerum biomarkers as neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enabled early identification of multiple sclerosis (MS) patients at risk of relapse-associated worsening (RAW) or progression independent of relapses (PIRA). However, the immunological mechanisms underlying these clinical phenotypes remain unclear.MethodsWe conducted a cross-sectional study including 117 MS patients and 84 healthy controls (HC). Patients were stratified as NLGL (low sNfL and sGFAP), NH (high sNfL at different levels of sGFAP), and NLGH (low sNfL and high sGFAP). Percentages of blood and cerebrospinal fluid (CSF) mononuclear cells, and intracellular production of cytokines by T and B cells after “in vitro” stimulation were analyzed by flow cytometry.ResultsWe identified a common inflammatory profile present in the blood of all MS groups comprising significant increases of effector CD4+ and CD8+ T cells, of memory and antigen-presenting B cells, of CD4+ and CD8+ T cells producing interferon-gamma, interleukin-17 and tumor necrosis factor-alpha (TNF-α) and of B cells producing TNF-α. Additionally, the highly inflammatory NH group showed lower frequencies of different regulatory subsets (transitional B cells, PDL1+ monocytes and Treg cells) compared to HC and increased percentages of CD4+ and CD8+ T cells producing granulocyte-macrophage colony-stimulating factor and of effector CD56dim NK cells. They also showed lower percentages of Treg in blood and CSF compared to the low inflammatory NLGL group, which also displayed higher frequencies of regulatory CD56dim, NKG2A+ cells.ConclusionAll MS patients share increased inflammatory B and T cells, but differ in regulatory or NK subsets, which identify highly inflammatory or benign disease courses.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1648725/fullmultiple sclerosisserum biomarkerscellular phenotype and functionneurofilament light chainglial fibrillary acidic proteindemyelinating disease of central nervous system |
| spellingShingle | Alexander Rodero-Romero José Ignacio Fernández-Velasco Enric Monreal Raquel Sainz-Amo Roberto Álvarez-Lafuente Manuel Comabella Manuel Comabella Lluís Ramió-Torrentà Lluís Ramió-Torrentà Lluís Ramió-Torrentà José M. García-Domínguez Noelia Villarrubia Susana Sainz de la Maza María Domínguez-Mozo Ana Quiroga-Varela Juan Luís Chico-García Fernando Rodriguez-Jorge José Luis Veiga-Gonzalez Ernesto Roldán-Santiago Mercedes Espiño Eulalia Rodríguez-Martín Gary Álvarez Jaime Masjuan Xavier Montalban Xavier Montalban Lucienne Costa-Frossard Luisa María Villar Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis Frontiers in Immunology multiple sclerosis serum biomarkers cellular phenotype and function neurofilament light chain glial fibrillary acidic protein demyelinating disease of central nervous system |
| title | Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis |
| title_full | Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis |
| title_fullStr | Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis |
| title_full_unstemmed | Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis |
| title_short | Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis |
| title_sort | identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis |
| topic | multiple sclerosis serum biomarkers cellular phenotype and function neurofilament light chain glial fibrillary acidic protein demyelinating disease of central nervous system |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1648725/full |
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