title: Sera from neuromyelitis optica patients disrupt the blood-brain barrier.
abstract: OBJECTIVE
  In neuromyelitis optica (NMO), the destruction of the blood-brain barrier (BBB) has been considered to be the first step of the disease process. It is unclear whether sera from patients with NMO can open the BBB, and which component of patient sera is most important for this disruption.
  
  
  METHODS
  The effects of sera from antiaquaporin4 (AQP4) antibody positive NMO patients, multiple sclerosis patients and control subjects were evaluated for expression of tight junction proteins and for transendothelial electrical resistance (TEER) of human brain microvascular endothelial cells (BMECs). Whether antibodies against human BMECs as well as anti-AQP4 antibodies exist in NMO sera was also examined using western blot analysis.
  
  
  RESULTS
  Expression of tight junction proteins and TEER in BMECs was significantly decreased after exposure to NMO sera. However, this effect was reversed after application of an antivascular endothelial growth factor (VEGF) neutralising antibody. Antibodies against BMECs other than anti-AQP4 antibodies were found in the sera of NMO patients whereas no specific bands were detected in the sera of healthy and neurological controls. These antibodies apparently disrupt the BBB by increasing the autocrine secretion of VEGF by BMECs themselves. Absorption of the anti-AQP4 antibody by AQP4 transfected astrocytes reduced AQP4 antibody titres but was not associated with a reduction in BBB disruption.
  
  
  CONCLUSIONS
  Sera from NMO patients reduce expression of tight junction proteins and disrupt the BBB. Autoantibodies against BMECs other than anti-AQP4 antibodies may disrupt the BBB through upregulation of VEGF in BMECs.
authors.affiliation: Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Shimizu
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Sano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Haruki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Saito
authors.forename: Michiaki
authors.initials: M
authors.lastname: Koga
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanda
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001812:Blood-Brain Barrier / Q000276:immunology; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000276:immunology; D006801:Humans; D009471:Neuromyelitis Optica / Q000097:blood / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D016207:Cytokines