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Systemic complement profiling in multiple sclerosis as a biomarker of disease state

Ingram, Gillian, Hakobyan, Svetlana, Hirst, Claire Louise, Harris, Claire Louise, Loveless, Samantha ORCID:, Mitchell, John Paul, Pickersgill, Trevor, Robertson, Neil ORCID: and Morgan, Bryan Paul ORCID: 2012. Systemic complement profiling in multiple sclerosis as a biomarker of disease state. Multiple Sclerosis Journal 18 (10) , pp. 1401-1411. 10.1177/1352458512438238

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Background: There is increasing evidence of significant and dynamic systemic activation and upregulation of complement in multiple sclerosis (MS), which may contribute to disease pathogenesis. Objective: We aimed to investigate the pathological role of complement in MS and the potential role for complement profiling as a biomarker of MS disease state. Methods: Key components of the classical, alternative and terminal pathways of complement were measured in plasma and cerebrospinal fluid (CSF) of patients with MS in different clinical phases of disease and in matched controls. Results: Increased plasma levels of C3 (p<0.003), C4 (p<0.001), C4a (p<0.001), C1 inhibitor (p<0.001), and factor H (p<0.001), and reduced levels of C9 (p<0.001) were observed in MS patients compared with controls. Combined profiling of these analytes produced a statistical model with a predictive value of 97% for MS and 73% for clinical relapse when combined with selected demographic data. CSF-plasma correlations suggested that source of synthesis of these components was both systemic and central. Conclusion: These data provide further evidence of alterations in both local and systemic expression and activation of complement in MS and suggest that complement profiling may be informative as a biomarker of MS disease, although further work is needed to determine its use in distinguishing MS from its differential.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: multiple sclerosis, demyelination, biomarkers, complement, immunology
Publisher: Sage
ISSN: 1352-4585
Date of First Compliant Deposit: 30 March 2016
Last Modified: 09 May 2024 20:38

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