title: Homogeneity of active demyelinating lesions in established multiple sclerosis.
abstract: OBJECTIVE
  Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS.
  
  
  METHODS
  All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging-guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions.
  
  
  RESULTS
  Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found.
  
  
  CONCLUSIONS
  The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fcgamma receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS.
authors.affiliation: Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Esther C W
authors.initials: EC
authors.lastname: Breij
authors.forename: Bianca P
authors.initials: BP
authors.lastname: Brink
authors.forename: Rob
authors.initials: R
authors.lastname: Veerhuis
authors.forename: Christa
authors.initials: C
authors.lastname: van den Berg
authors.forename: Rianka
authors.initials: R
authors.lastname: Vloet
authors.forename: Riqiang
authors.initials: R
authors.lastname: Yan
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: Lars
authors.initials: L
authors.lastname: Bö
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000032:analysis / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018992:Myelin-Associated Glycoprotein / Q000032:analysis / Q000276:immunology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009836:Oligodendroglia / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007074:Immunoglobulin G; D018992:Myelin-Associated Glycoprotein; D003165:Complement System Proteins