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Research paper
Blood–brain barrier destruction determines Fisher/Bickerstaff clinical phenotypes: an in vitro study
  1. Kazuyuki Saito1,2,
  2. Fumitaka Shimizu1,
  3. Michiaki Koga1,
  4. Yasuteru Sano1,
  5. Ayako Tasaki1,
  6. Masaaki Abe1,
  7. Hiroyo Haruki1,
  8. Toshihiko Maeda1,
  9. Seiko Suzuki3,
  10. Susumu Kusunoki3,
  11. Hidehiro Mizusawa2,
  12. Takashi Kanda1
  1. 1Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
  2. 2Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medicine, Bunkyo, Tokyo, Japan
  3. 3Department of Neurology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
  1. Correspondence to Dr Takashi Kanda, Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi 7558505, Japan; tkanda{at}yamaguchi-u.ac.jp

Abstract

Objective To ascertain the hypothesis that the phenotypic differences between Bickerstaff's brainstem encephalitis (BBE) and Miller Fisher syndrome (MFS) are derived from the differences in the effects of sera on blood–brain barrier (BBB) and blood–nerve barrier.

Background Antibodies against GQ1b are frequently detected in BBE and MFS, and these two disorders may share the same pathogenesis, but the clinical phenotypes of BBE and MFS are substantially different.

Methods The effects of sera obtained from BBE patients, MFS patients and control subjects were evaluated with regard to the expression of tight junction proteins and transendothelial electrical resistance in human brain microvascular endothelial cells (BMECs) and human peripheral nerve microvascular endothelial cells.

Results The sera obtained from BBE patients decreased the transendothelial electrical resistance values and claudin-5 protein expression in BMECs, although the sera obtained from MFS patients had no effect on BMECs or peripheral nerve microvascular endothelial cells. This effect was reversed after the application of matrix metalloproteinase (MMP) inhibitor, GM6001. The presence or absence of anti-GQ1b antibodies did not significantly influence the results. MMP-9 secreted by BMECs was significantly increased after exposure to the sera obtained from BBE patients, whereas it was not changed after exposure to the sera obtained from MFS patients.

Conclusions Only the sera obtained from BBE patients destroyed BBB and it might explain the phenotypical differences between BBE and MFS. BBE sera disrupted BBB, possibly via the autocrine secretion of MMP-9 from BBB-composing endothelial cells.

  • GUILLAIN-BARRE SYNDROME
  • BLOOD-BRAIN BARRIER
  • GANGLIOSIDE
  • NEUROIMMUNOLOGY

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