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Clinical and biochemical analysis of the prognostic relevance of biomarkers in multiple sclerosis

Ingram, Gillian 2011. Clinical and biochemical analysis of the prognostic relevance of biomarkers in multiple sclerosis. PhD Thesis, Cardiff University.

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Abstract

The work in this thesis was initiated by the development of an extensive serum, plasma, cerebrospinal fluid (CSF) and deoxyribonucleic acid (DNA) multiple sclerosis (MS) disease and control biobank, with samples linked to extensive longitudinal clinical information. The biobank was designed to be utilised with the aim of identifying serum, plasma, CSF and genetic biomarkers for MS. Further, to examine the relevance of potential biomarkers to disease ignition, disease course and progression, response to treatment and ability to predict prognosis in patients with MS, comparing markers to clinical phenotype and non-neurological controls. I elected to investigate various components, fragments and regulators of the complement (C) system based on work showing C to be an important player in MS and in other neuroinflammatory diseases. An initial pilot study examined serum C regulator factor H (fH) in MS disease subgroups and showed differential expression of fH in patients with progressive disease compared to patients with relapsing remitting disease and controls. These initial results were expanded demonstrating fH as a potentially sensitive and specific biomarker of disease course subgroups. Further, this thesis examines other complement proteins, fragments and regulators in plasma so as to build patient complement profiles specific to, and therefore biomarkers of, disease states. In an attempt to further knowledge in relation to the expression and extent of C activation in MS, the thesis examines C in CSF and then immunohistochemically in brain and spinal cord tissue showing up-regulation of C in relation to MS plaques throughout disease course. This work has identified a novel serum biomarker of MS disease course and patterns of C markers which provide biomarkers of MS and disease state. Up-regulation of C in MS and deposition within white matter plaques, implies a pathogenic role for C in MS.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
ISBN: 9781303222313
Date of First Compliant Deposit: 30 March 2016
Last Modified: 05 Jun 2017 04:17
URI: http://orca-mwe.cf.ac.uk/id/eprint/55077

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