Complement regulator factor H as a serum biomarker of multiple sclerosis disease state

Ingram, Gillian, Hakobyan, Svetlana, Hirst, Claire Louise, Harris, Claire Louise, Pickersgill, Trevor, Cossburn, Mark D., Loveless, Samantha ORCID: https://orcid.org/0000-0002-5124-4115, Robertson, Neil ORCID: https://orcid.org/0000-0002-5409-4909 and Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676 2010. Complement regulator factor H as a serum biomarker of multiple sclerosis disease state. Brain 133 (6) , pp. 1602-1611. 10.1093/brain/awq085

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Abstract

Multiple sclerosis has a variable phenotypic presentation and subsequent disease course that, although unpredictable at disease onset, is of crucial importance in guiding interventions. Effective and accessible biomarkers are required in order to stratify patients and inform treatment. We examined whether the complement regulator factor H and its Tyr402His polymorphism, recently implicated as biomarkers in other chronic inflammatory central nervous system conditions, might identify or predict specific pathological processes and outcomes in multiple sclerosis. Employing novel assays, we measured factor H and its His402 variant in serum from 350 patients with multiple sclerosis classified according to disease course and relapse status. Serum factor H levels were significantly higher in progressive disease (P < 0.001) compared to controls and relapsing patients, after controlling for variables including disease duration, age, gender, disability and treatment. Serum factor H levels were capable of distinguishing secondary progressive from relapsing remitting disease (excluding patients in clinical relapse) with a sensitivity of 89.41%, specificity of 69.47% and a positive predictive value of 72.38%. Acute relapse was also associated with transiently increased factor H levels (P = 0.009) compared to stable relapsing disease. In clinically stable patients, factor H levels remained constant over 1 year (coefficient of variation percentage = 6.8), however, in patients in transition from relapsing to progressive disease, factor H levels significantly increased over a period of 2 years (P = 0.007). Concentration of the His402 variant in heterozytgotes was significantly higher in secondary progressive (P < 0.01) and primary progressive (P < 0.05) disease, suggesting altered expression or consumption of variants when factor H is upregulated. Serum factor H may be an effective indicator of progression and a practical and accessible biomarker and stratifying tool in determining disease course, providing objective evidence to help guide therapeutic decisions.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	factor H; complement; multiple sclerosis; biomarker; alternative pathway
Publisher:	Oxford University Press
ISSN:	0006-8950
Last Modified:	06 Nov 2022 13:17
URI:	https://orca.cardiff.ac.uk/id/eprint/26575

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