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Sera from neuromyelitis optica patients disrupt the blood–brain barrier — Shimizu et al. — Journal of Neurology, Neurosurgery & Psychiatry

Research paper

Sera from neuromyelitis optica patients disrupt the blood–brain barrier

Fumitaka Shimizu1,
Yasuteru Sano1,
Toshiyuki Takahashi2,
Hiroyo Haruki1,
Kazuyuki Saito1,
Michiaki Koga1,
Takashi Kanda1

+ Author Affiliations

1Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan

2Department of Neurology, Tohoku University Graduate School of Medicine, Miyagi, Japan

Correspondence to Dr T Kanda, Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi 7558505, Japan; tkanda@yamaguchi-u.ac.jp

Contributors FS and TK conceived and designed the study. All authors reviewed, amended and agreed on the final version of the manuscript.

Received 3 May 2011
Accepted 20 September 2011
Published Online First 19 November 2011

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.

Read More: Sera from neuromyelitis optica patients disrupt the blood–brain barrier — Shimizu et al. — Journal of Neurology, Neurosurgery & Psychiatry

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