Sera from patients with multifocal motor neuropathy disrupt the blood-nerve barrier.
OBJECTIVE
In multifocal motor neuropathy (MMN), the destruction of the blood-nerve barrier (BNB) has been considered to be the key step in the disease process. The purpose of the present study was to ascertain whether sera from patients with MMN can open the BNB, and which component of patient sera is the most important for this disruption.


METHODS
We evaluated the effects of sera from patients with MMN, patients with amyotrophic lateral sclerosis, and control subjects on the expression of tight junction proteins and vascular cell adhesion molecule-1 (VCAM-1), and on the transendothelial electrical resistance (TEER) in human peripheral nerve microvascular endothelial cells (PnMECs).


RESULTS
The sera from patients with MMN decreased the claudin-5 protein expression and the TEER in PnMECs. However, this effect was reversed after application of an anti-vascular endothelial growth factor (anti-VEGF) neutralising antibody. The VEGF secreted by PnMECs was significantly increased after exposure to the sera from patients with MMN. The sera from patients with MMN also increased the VCAM-1 protein expression by upregulating the nuclear factor kappa-B (NF-κB) signalling. The immunoglobulin G purified from MMN sera decreased the expression of claudin-5 and increased the VCAM-1 expression in PnMECs.


CONCLUSIONS
The sera from MMN patients may disrupt the BNB function via the autocrine secretion of VEGF in PnMECs, or the exposure to autoantibodies against PnMECs that are contained in the MMN sera. Autoantibodies against PnMECs in MMN sera may activate the BNB by upregulating the VCAM-1 expression, thereby allowing for the entry of a large number of circulating inflammatory cells into the peripheral nervous system.
Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, , Ube, Yamaguchi, Japan.
Fumitaka
F
Shimizu
Masatoshi
M
Omoto
Yasuteru
Y
Sano
Naoko
N
Mastui
Ai
A
Miyashiro
Ayako
A
Tasaki
Toshihiko
T
Maeda
Michiaki
M
Koga
Ryuji
R
Kaji
Takashi
T
Kanda
D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049428:Blood-Nerve Barrier / Q000503:physiopathology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D017097:Electric Impedance; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D044967:Serum / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D055815:Young Adult
D019010:Vascular Cell Adhesion Molecule-1
BLOOD-BRAIN BARRIER; IMMUNOLOGY; NEUROCHEMISTRY; NEUROMUSCULAR; NEUROPATHY