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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2025 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:dnet:uabarcelona_::1c578ac128f1622bcf3d008e03de1815 |
| Online Access: | https://ddd.uab.cat/record/328389 https://dx.doi.org/urn:doi:10.3390/ijms26146898 |
| Access Level: | Open access |
| Keyword: | Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
| _version_ | 1878736165458149376 |
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| author | Monreal, Enric|||0000-0003-3293-0125 |
| 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 |
| author_browse | Aladro, Yolanda|||0000-0001-9459-5452 Ayuso-Peralta, Lucía Chico-García, Juan Luís Comabella López, Manuel|||0000-0002-2373-6657 Costa-Frossard, Lucienne|||0000-0002-6512-4413 Cuello, Juan Pablo Espiño, Mercedes Fernández Velasco, José Ignacio|||0000-0001-9148-671X García Domínguez, José Manuel Llufriu, Sara|||0000-0003-4273-9121 Martín Ávila, Guillermo Martínez-Ginés, María Luisa Masjuan, Jaime|||0000-0003-1329-0943 Monreal, Enric|||0000-0003-3293-0125 Montalban, Xavier|||0000-0002-0098-9918 Pilo, Belén Quiroga-Varela, Ana Rodero-Romero, Alexander Rodríguez-Jorge, Fernando Rodríguez-Martín, Eulalia Roldán, Ernesto Rubio, Lluïsa Sainz De La Maza, Susana Veiga-Gonzalez, José Luis Villar, Luisa M.|||0000-0002-9067-3668 Villarrubia, Noelia Álvarez-Bravo, Gary |
| 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 |
| collection | Dipòsit Digital de Documents de la UAB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_8a2f8e4750df3ea2e1dcc89b31cd775a |
| institution | Universitat Autònoma de Barcelona |
| instname_str | Universitat Autònoma de Barcelona |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:dnet:uabarcelona_::1c578ac128f1622bcf3d008e03de1815 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| reponame_str | Dipòsit Digital de Documents de la UAB |
| spelling | Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis 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 Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression 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. https://ddd.uab.cat/record/328389 https://dx.doi.org/urn:doi:10.3390/ijms26146898 |
| 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 | 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_short | 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 |
| topic | Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
| topic_facet | Multiple sclerosis Neurofilament light chain Glial fibrillary acidic protein intrathecal IgM synthesis Progression |
| url | https://ddd.uab.cat/record/328389 https://dx.doi.org/urn:doi:10.3390/ijms26146898 |