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Research paper
Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy
  1. Fumitaka Shimizu1,
  2. Mariko Oishi1,
  3. Setsu Sawai2,
  4. Minako Beppu2,
  5. Sonoko Misawa2,
  6. Naoko Matsui3,
  7. Ai Miyashiro3,
  8. Toshihiko Maeda1,
  9. Yukio Takeshita1,
  10. Hideaki Nishihara1,
  11. Yasuteru Sano1,
  12. Ryota Sato1,
  13. Ryuji Kaji3,
  14. Satoshi Kuwabara2,
  15. Takashi Kanda1
  1. 1 Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan
  2. 2 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
  3. 3 Department of Clinical Neuroscience, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
  1. Correspondence to Dr Takashi Kanda, Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube 7558505, Japan; tkanda{at}yamaguchi-u.ac.jp

Abstract

Objective 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.

Methods 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.

Results 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.

Conclusion 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.

  • chronic inflammatory demyelinating polyneuropathy
  • multifocal motor neuropathy
  • blood-nerve barrier
  • IP-10
  • conduction block

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Footnotes

  • Contributors FS and TK were responsible for conception and design of the study. FS performed the experiments, analysed and interpreted the data, and wrote the manuscript. MO, HN, YS, TM, RS and YT performed the experiments and analysed the data. FS, MO, SS, MB, SM, AM and NM were responsible for collecting sample and clinical data from patients. SK, RK and TK edited the manuscript.

  • Funding The funding organisations had no role in the design or conduct of this research. This work was supported most by research grants (J29008) from Yamaguchi University. This work was supported in part by a research grant (K2529006) from the Japan Society for the Promotion of Science, Tokyo, Japan, research grants (18K07526 and 17H04197) from Health and Labour Sciences Research Grants for research on intractable diseases (Neuroimmunological Disease Research Committee) from the Ministry of Health, Labour and Welfare of Japan, an Intramural Research Grant (25-4) for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry, Novartis research grant (J29018), and Takeda research foundation (J29025).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the ethics committee of the Yamaguchi University Medical Faculty in accordance with the principles of the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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