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Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 1937

Special Issue Editor


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Guest Editor
Department of Medicine, Neurology Division, University of Saskatchewan, Saskatoon, SK S7N 0X8, Canada
Interests: neurology; neuroscience; multiple sclerosis; RNA-binding proteins; neurodegeneration
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue on “Insights in Multiple Sclerosis (MS) and Neuroimmunology”.

Neurodegeneration, defined as damage to neurons, oligodendrocytes, and axons, is now acknowledged to be the primary driver of disability in multiple sclerosis (MS) patients. Therefore, research into the mechanisms of neurodegeneration in MS has expanded over the past several years. Furthermore, with the development and implementation of more precise technologies, including sequencing and advanced imaging, we can more confidently define processes that cause damage to neurons, oligodendrocytes, and axons in MS.

For this Special Issue on ‘Insights in Multiple Sclerosis (MS) and Neuroimmunology’, we accept both reviews and original articles that explore the mechanisms of neurodegeneration, including those with an immunological mediator (i.e., macrophages, T-cells, B-cells, astrocytes, etc.). Reviews should highlight the most recent findings with regard to this topic, as well as emphasize novel approaches that are helping to advance this area of research. Original articles should demonstrate potential mechanisms of neurodegeneration, including damage to neurons, oligodendrocytes, and axons, in any MS models, including in vitro, in vivo, and in situ systems with a particular emphasis on immunological mediators. Original articles may also include potential therapies to combat neurodegeneration in MS.

This Special Issue is supervised by Prof. Dr. Michael C. Levin and assisted by Dr. Catherine Hutchinson. We warmly welcome the submission of short communications, original research articles, and review articles.

Prof. Dr. Michael C. Levin
Guest Editor

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Keywords

  • neurodegeneration
  • neuroimmunology
  • macrophage
  • T-cell
  • B-cell
  • antibody
  • neurons
  • oligodendrocytes
  • axon
  • axonal damage
  • cell death
  • multiple sclerosis

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Published Papers (2 papers)

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Research

20 pages, 1676 KiB  
Article
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis
by Enric Monreal, José Ignacio Fernández-Velasco, Susana Sainz de la Maza, Mercedes Espiño, Noelia Villarrubia, Ernesto Roldán-Santiago, Yolanda Aladro, Juan Pablo Cuello, Lucía Ayuso-Peralta, Alexander Rodero-Romero, Juan Luís Chico-García, Fernando Rodríguez-Jorge, Ana Quiroga-Varela, Eulalia Rodríguez-Martín, Belén Pilo de la Fuente, Guillermo Martín-Ávila, María Luisa Martínez-Ginés, José Manuel García-Domínguez, Lluïsa Rubio, Sara Llufriu, Manuel Comabella, Xavier Montalban, Gary Álvarez-Bravo, José Luís Veiga-González, Jaime Masjuan, Lucienne Costa-Frossard and Luisa María Villaradd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(14), 6898; https://doi.org/10.3390/ijms26146898 - 18 Jul 2025
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
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13 pages, 1914 KiB  
Article
Profiling Blood-Based Neural Biomarkers and Cytokines in Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Using Single-Molecule Array Technology
by Insha Zahoor, Sajad Mir and Shailendra Giri
Int. J. Mol. Sci. 2025, 26(7), 3258; https://doi.org/10.3390/ijms26073258 - 1 Apr 2025
Cited by 1 | Viewed by 766
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based analytes, including cytokines and neural biomarkers are the predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in [...] Read more.
Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based analytes, including cytokines and neural biomarkers are the predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in reports on EAE across animal strains/studies, limiting the utility of these biomarkers for predicting disease activity. In this study, we investigated blood-based analyte profiles, including neural markers (NFL and GFAP) and cytokines (IL-6, IL-17, IL-12p70, IL-10, and TNF-α), in two clinically distinct EAE models: relapsing-remitting (RR)-EAE and chronic-EAE. Ultrasensitive single-molecule array technology (SIMOA, Quanterix) was used to profile the analytes in the blood plasma of mice at the acute, chronic, and progressive phases of disease. In both models, NFL was substantially increased during post-disease onset across all phases, with a pronounced increase observed in chronic-EAE. The leakage of GFAP into peripheral blood was also greater after disease onset in both EAE models, especially in the acute phase of chronic-EAE. Among all cytokines, only IL-10 had consistently lower levels in both EAE models throughout the course of disease. This study suggests NFL, GFAP, and IL-10 as potential translational predictors of disease activity in EAE, making them potential candidates as surrogate markers for the preclinical testing of therapeutic interventions in animal models of MS. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
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