title: Complement activation in multiple sclerosis plaques: an immunohistochemical analysis.
abstract: BACKGROUND
  Inflammation and complement activation are firmly implicated in the pathology of multiple sclerosis; however, the extent and nature of their involvement in specific pathological processes such as axonal damage, myelin loss and disease progression remains uncertain. This study aims to bring clarity to these questions.
  
  
  RESULTS
  We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive multiple sclerosis and 16 control donors, including 9 with central nervous system disease. Active, chronic active and chronic inactive multiple sclerosis plaques (35 in total) and non-plaque areas were examined.Multiple sclerosis plaques were consistently positive for complement proteins (C3, factor B, C1q), activation products (C3b, iC3b, C4d, terminal complement complex) and regulators (factor H, C1-inhibitor, clusterin), suggesting continuing local complement synthesis, activation and regulation despite the absence of other evidence of ongoing inflammation. Complement staining was most apparent in plaque and peri-plaque but also present in normal appearing white matter and cortical areas to a greater extent than in control tissue. C1q staining was present in all plaques suggesting a dominant role for the classical pathway. Cellular staining for complement components was largely restricted to reactive astrocytes, often adjacent to clusters of microglia in close apposition to complement opsonised myelin and damaged axons.
  
  
  CONCLUSIONS
  The findings demonstrate the ubiquity of complement involvement in multiple sclerosis, suggest a pathogenic role for complement contributing to cell, axon and myelin damage and make the case for targeting complement for multiple sclerosis monitoring and therapy.
authors.forename: Gillian
authors.initials: G
authors.lastname: Ingram
authors.forename: Sam
authors.initials: S
authors.lastname: Loveless
authors.forename: Owain W
authors.initials: OW
authors.lastname: Howell
authors.forename: Svetlana
authors.initials: S
authors.lastname: Hakobyan
authors.forename: Bethan
authors.initials: B
authors.lastname: Dancey
authors.forename: Claire L
authors.initials: CL
authors.lastname: Harris
authors.forename: Neil P
authors.initials: NP
authors.lastname: Robertson
authors.forename: James W
authors.initials: JW
authors.lastname: Neal
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. morganbp@cardiff.ac.uk.
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003167:Complement Activation / Q000502:physiology*; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D003165:Complement System Proteins