Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis
The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:dnet:uabarcelona_::1c578ac128f1622bcf3d008e03de1815 |
| Acceso en línea: | https://ddd.uab.cat/record/328389 https://dx.doi.org/urn:doi:10.3390/ijms26146898 |
| Access Level: | acceso abierto |
| Palabra clave: | Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
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Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple SclerosisMonreal, Enric|||0000-0003-3293-0125Fernández Velasco, José Ignacio|||0000-0001-9148-671XSainz De La Maza, SusanaEspiño, MercedesVillarrubia, NoeliaRoldán, ErnestoAladro, Yolanda|||0000-0001-9459-5452Cuello, Juan PabloAyuso-Peralta, LucíaRodero-Romero, AlexanderChico-García, Juan LuísRodríguez-Jorge, FernandoQuiroga-Varela, AnaRodríguez-Martín, EulaliaPilo, BelénMartín Ávila, GuillermoMartínez-Ginés, María LuisaGarcía Domínguez, José ManuelRubio, LluïsaLlufriu, Sara|||0000-0003-4273-9121Comabella López, Manuel|||0000-0002-2373-6657Montalban, Xavier|||0000-0002-0098-9918Álvarez-Bravo, GaryVeiga-Gonzalez, José LuisMasjuan, Jaime|||0000-0003-1329-0943Costa-Frossard, Lucienne|||0000-0002-6512-4413Villar, Luisa M.|||0000-0002-9067-3668Multiple sclerosisNeurofilament light chainGlial fibrillary acidic proteinintrathecal IgM synthesisProgressionThe combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB-positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB-negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/328389https://dx.doi.org/urn:doi:10.3390/ijms26146898reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00828Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/01018Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0001Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0002Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0003Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0006open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::1c578ac128f1622bcf3d008e03de18152026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| title |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| spellingShingle |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis Monreal, Enric|||0000-0003-3293-0125 Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
| title_short |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| title_full |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| title_fullStr |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| title_full_unstemmed |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| title_sort |
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis |
| dc.creator.none.fl_str_mv |
Monreal, Enric|||0000-0003-3293-0125 Fernández Velasco, José Ignacio|||0000-0001-9148-671X Sainz De La Maza, Susana Espiño, Mercedes Villarrubia, Noelia Roldán, Ernesto Aladro, Yolanda|||0000-0001-9459-5452 Cuello, Juan Pablo Ayuso-Peralta, Lucía Rodero-Romero, Alexander Chico-García, Juan Luís Rodríguez-Jorge, Fernando Quiroga-Varela, Ana Rodríguez-Martín, Eulalia Pilo, Belén Martín Ávila, Guillermo Martínez-Ginés, María Luisa García Domínguez, José Manuel Rubio, Lluïsa Llufriu, Sara|||0000-0003-4273-9121 Comabella López, Manuel|||0000-0002-2373-6657 Montalban, Xavier|||0000-0002-0098-9918 Álvarez-Bravo, Gary Veiga-Gonzalez, José Luis Masjuan, Jaime|||0000-0003-1329-0943 Costa-Frossard, Lucienne|||0000-0002-6512-4413 Villar, Luisa M.|||0000-0002-9067-3668 |
| author |
Monreal, Enric|||0000-0003-3293-0125 |
| author_facet |
Monreal, Enric|||0000-0003-3293-0125 Fernández Velasco, José Ignacio|||0000-0001-9148-671X Sainz De La Maza, Susana Espiño, Mercedes Villarrubia, Noelia Roldán, Ernesto Aladro, Yolanda|||0000-0001-9459-5452 Cuello, Juan Pablo Ayuso-Peralta, Lucía Rodero-Romero, Alexander Chico-García, Juan Luís Rodríguez-Jorge, Fernando Quiroga-Varela, Ana Rodríguez-Martín, Eulalia Pilo, Belén Martín Ávila, Guillermo Martínez-Ginés, María Luisa García Domínguez, José Manuel Rubio, Lluïsa Llufriu, Sara|||0000-0003-4273-9121 Comabella López, Manuel|||0000-0002-2373-6657 Montalban, Xavier|||0000-0002-0098-9918 Álvarez-Bravo, Gary Veiga-Gonzalez, José Luis Masjuan, Jaime|||0000-0003-1329-0943 Costa-Frossard, Lucienne|||0000-0002-6512-4413 Villar, Luisa M.|||0000-0002-9067-3668 |
| author_role |
author |
| author2 |
Fernández Velasco, José Ignacio|||0000-0001-9148-671X Sainz De La Maza, Susana Espiño, Mercedes Villarrubia, Noelia Roldán, Ernesto Aladro, Yolanda|||0000-0001-9459-5452 Cuello, Juan Pablo Ayuso-Peralta, Lucía Rodero-Romero, Alexander Chico-García, Juan Luís Rodríguez-Jorge, Fernando Quiroga-Varela, Ana Rodríguez-Martín, Eulalia Pilo, Belén Martín Ávila, Guillermo Martínez-Ginés, María Luisa García Domínguez, José Manuel Rubio, Lluïsa Llufriu, Sara|||0000-0003-4273-9121 Comabella López, Manuel|||0000-0002-2373-6657 Montalban, Xavier|||0000-0002-0098-9918 Álvarez-Bravo, Gary Veiga-Gonzalez, José Luis Masjuan, Jaime|||0000-0003-1329-0943 Costa-Frossard, Lucienne|||0000-0002-6512-4413 Villar, Luisa M.|||0000-0002-9067-3668 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
| topic |
Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
| description |
The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB-positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB-negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2 2025-01-01 2025 2025-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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info:eu-repo/semantics/article |
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article |
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https://ddd.uab.cat/record/328389 https://dx.doi.org/urn:doi:10.3390/ijms26146898 |
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https://ddd.uab.cat/record/328389 https://dx.doi.org/urn:doi:10.3390/ijms26146898 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
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Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00828 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/01018 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0001 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0002 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0003 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0015/0006 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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