Blood–brain barrier destruction determines Fisher/Bickerstaff clinical phenotypes: an in vitro study

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 84; no. 7; pp. 756 - 765
• Main Authors: Saito, Kazuyuki, Shimizu, Fumitaka, Koga, Michiaki, Sano, Yasuteru, Tasaki, Ayako, Abe, Masaaki, Haruki, Hiroyo, Maeda, Toshihiko, Suzuki, Seiko, Kusunoki, Susumu, Mizusawa, Hidehiro, Kanda, Takashi
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.07.2013; BMJ Publishing Group LTD
• Subjects: Antibodies; Antibodies, Blocking - pharmacology; Antibodies, Blocking - therapeutic use; Ataxia; BLOOD-BRAIN BARRIER; Blood-Brain Barrier - pathology; Blood-Nerve Barrier - pathology; Blotting, Western; Capillaries - pathology; Cells, Cultured; Dipeptides - pharmacology; Electric Impedance; Encephalitis - blood; Encephalitis - pathology; Endothelial Cells - metabolism; Enzyme-Linked Immunosorbent Assay; GANGLIOSIDE; GUILLAIN-BARRE SYNDROME; Humans; Immunoglobulin G - isolation & purification; Indicators and Reagents; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - metabolism; Membranes; Miller Fisher Syndrome - blood; Miller Fisher Syndrome - metabolism; Miller Fisher Syndrome - pathology; Nervous system; NEUROIMMUNOLOGY; Patients; Phenotype; Protease Inhibitors - pharmacology; Serum; Tight Junctions - physiology; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Minnesota; California; United Kingdom > UK; United States > US; GUILLAIN-BARRE SYNDROME; BLOOD-BRAIN BARRIER; GANGLIOSIDE; NEUROIMMUNOLOGY
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp-2012-304306

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.