Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis

• Published in: International journal of molecular sciences Vol. 26; no. 14; p. 6898
• Main Authors: Monreal, Enric, Fernández-Velasco, José Ignacio, Sainz de la Maza, Susana, Espiño, Mercedes, Villarrubia, Noelia, Roldán-Santiago, Ernesto, Aladro, Yolanda, Cuello, Juan Pablo, Ayuso-Peralta, Lucía, Rodero-Romero, Alexander, Chico-García, Juan Luís, Rodríguez-Jorge, Fernando, Quiroga-Varela, Ana, Rodríguez-Martín, Eulalia, Pilo de la Fuente, Belén, Martín-Ávila, Guillermo, Martínez-Ginés, María Luisa, García-Domínguez, José Manuel, Rubio, Lluïsa, Llufriu, Sara, Comabella, Manuel, Montalban, Xavier, Álvarez-Bravo, Gary, Veiga-González, José Luís, Masjuan, Jaime, Costa-Frossard, Lucienne, Villar, Luisa María
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.07.2025; MDPI
• Subjects: Adult; B cells; Biological markers; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Disability; Disease Progression; Female; Glial Fibrillary Acidic Protein - blood; Glial Fibrillary Acidic Protein - cerebrospinal fluid; Humans; Immunology; Lymphocytes; Male; Medical research; Medicine, Experimental; Middle Aged; Multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - diagnosis; Neurofilament Proteins - blood; Neurofilament Proteins - cerebrospinal fluid; Ofatumumab; Oligoclonal Bands - blood; Oligoclonal Bands - cerebrospinal fluid; Prognosis; Regression analysis; T cells; Mississippi; Spain; progression; intrathecal IgM synthesis; neurofilament light chain; glial fibrillary acidic protein; multiple sclerosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms26146898

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.