Shimizu, Fumitaka Yamaguchi University
Oishi, Mariko Yamaguchi University
Sawai, Setsu Chiba University
Beppu, Minako Chiba University
Misawa, Sonoko Chiba University
Maeda, Toshihiko Yamaguchi University
Takeshita, Yukio Yamaguchi University
Nishihara, Hideaki Yamaguchi University
Sano, Yasuteru Yamaguchi University
Sato, Ryota Yamaguchi University
Kuwabara, Satoshi Chiba University
Kanda, Takashi Yamaguchi University
Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN.
We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system.
The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups.
The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN.
Journal of Neurology, Neurosurgery, and Psychiatry
BMJ Publishing Group
This article has been accepted for publication in Journal of Neurology, Neurosurgery, and Psychiatry, 2018 following peer review, and the Version of Record can be accessed online at https://doi.org/10.1136/jnnp-2018-319270.
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