Aims: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis.
Methods: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in three independent cohorts (n = 249), analyses its expression pattern in MS lesions (n = 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators.
Results: SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n = 81) and Switzerland (n = 92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC.
Conclusions: Conflicting results of SPARCL-1's differential expression in CSF of three independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/nan.12412 | DOI Listing |
J Clin Med
January 2025
Discipline of Neurology, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.
Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation and neurodegeneration. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown promise in reducing disease activity in MS patients. This prospective study aims to assess the effectiveness of ocrelizumab in reducing confirmed disability progression in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) over a two-year period.
View Article and Find Full Text PDFMedicina (Kaunas)
January 2025
Department of Neurology, Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
Early-onset MS (EOMS) and late-onset MS (LOMS) differ in terms of symptom presentation, disease progression, and disability outcomes. This study aims to evaluate the clinical characteristics of patients with EOMS and LOMS in Lithuania. A retrospective analysis of patients' medical records was conducted at the Lithuanian University of Health Sciences, Kaunas Clinics Department of Neurology.
View Article and Find Full Text PDFBiomedicines
November 2024
Virological Analysis and Reference Unit, National Medical Center "20 de Noviembre" Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City 03100, Mexico.
: Multiple sclerosis (MS) is a disease characterized by demyelination and axonal damage of the central nervous system. Despite the observed benefits, highly effective treatment (HET)-based therapy has adverse effects, which include an increased risk of developing progressive multifocal leukoencephalopathy (PML). Additionally, the risk grows if the patient has antibodies for the John Cunningham virus (JCV).
View Article and Find Full Text PDFMult Scler
January 2025
Departamento de Neurología, Pontificia Universidad Católica de Chile, Santiago, Chile.
Front Cell Neurosci
December 2024
Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.
Multiple sclerosis (MS), a debilitating autoimmune disorder targeting the central nervous system (CNS), is marked by relentless demyelination and inflammation. Clinically, it presents in three distinct forms: relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). While disease-modifying therapies (DMTs) offer some relief to people with RRMS, treatment options for progressive MS (pMS) remain frustratingly inadequate.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!