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Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.
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- Author(s): Khademi M;Khademi M; Dring AM; Gilthorpe JD; Wuolikainen A; Al Nimer F; Harris RA; Andersson M; Brundin L; Piehl F; Olsson T; Svenningsson A
- Source:
PloS one [PLoS One] 2013 May 07; Vol. 8 (5), pp. e63172. Date of Electronic Publication: 2013 May 07 (Print Publication: 2013).- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- Publication Information: Original Publication: San Francisco, CA : Public Library of Science
- Subject Terms: Biomarkers/*cerebrospinal fluid ; Central Nervous System/*pathology ; Inflammation/*cerebrospinal fluid ; Multiple Sclerosis/*cerebrospinal fluid; Aged ; Case-Control Studies ; Demography ; Humans ; Inflammation/pathology ; Least-Squares Analysis ; Models, Biological ; Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid ; Principal Component Analysis
- Abstract: Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS) neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS). The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066) using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9), chemokine (C-X-C motif) ligand 13 (CXCL13), osteopontin (OPN) and neurofilament-light chain (NFL) were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive), clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later disease stages.
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- Publication Date: Date Created: 20130514 Date Completed: 20131217 Latest Revision: 20240319
- Publication Date: 20240319
- Accession Number: PMC3646751
- Accession Number: 10.1371/journal.pone.0063172
- Accession Number: 23667585
- Source:
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