title: Systemic complement profiling in multiple sclerosis as a biomarker of disease state.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, University Hospital of Wales, Cardiff, UK.
authors.forename: G
authors.initials: G
authors.lastname: Ingram
authors.forename: S
authors.initials: S
authors.lastname: Hakobyan
authors.forename: C L
authors.initials: CL
authors.lastname: Hirst
authors.forename: C L
authors.initials: CL
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Loveless
authors.forename: J P
authors.initials: JP
authors.lastname: Mitchell
authors.forename: T P
authors.initials: TP
authors.lastname: Pickersgill
authors.forename: N P
authors.initials: NP
authors.lastname: Robertson
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003165:Complement System Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology
chemical_list: D015415:Biomarkers; D003165:Complement System Proteins