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August 20, 2013; 81 (8) Article

Anti-neurofascin antibody in patients with combined central and peripheral demyelination

Nobutoshi Kawamura, Ryo Yamasaki, Tomomi Yonekawa, Takuya Matsushita, Susumu Kusunoki, Shigemi Nagayama, Yasuo Fukuda, Hidenori Ogata, Dai Matsuse, Hiroyuki Murai, Jun-ichi Kira
First published July 24, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182a1aa9c
Nobutoshi Kawamura
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Ryo Yamasaki
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Tomomi Yonekawa
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Takuya Matsushita
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Susumu Kusunoki
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Shigemi Nagayama
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Yasuo Fukuda
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Hidenori Ogata
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Dai Matsuse
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Hiroyuki Murai
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Jun-ichi Kira
From the Departments of Neurology (N.K., T.Y., T.M., H.O., D.M., H.M., J.K.) and Neurological Therapeutics (R.Y.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (S.K.), School of Medicine, Kinki University, Osaka; Department of Neurology (S.N.), Kanazawa Medical University; and Department of Neurology (Y.F.), Sasebo City General Hospital, Japan.
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Citation
Anti-neurofascin antibody in patients with combined central and peripheral demyelination
Nobutoshi Kawamura, Ryo Yamasaki, Tomomi Yonekawa, Takuya Matsushita, Susumu Kusunoki, Shigemi Nagayama, Yasuo Fukuda, Hidenori Ogata, Dai Matsuse, Hiroyuki Murai, Jun-ichi Kira
Neurology Aug 2013, 81 (8) 714-722; DOI: 10.1212/WNL.0b013e3182a1aa9c

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Abstract

Objectives: We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD).

Methods: We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells.

Results: At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody–positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms.

Conclusion: Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange.

GLOSSARY

AIDP=
acute inflammatory demyelinating polyradiculoneuropathy;
AMAN=
acute motor axonal neuropathy;
Caspr=
contactin-associated protein 1;
CCPD=
combined central and peripheral demyelination;
CIDP=
chronic inflammatory demyelinating polyradiculoneuropathy;
GBS=
Guillain-Barré syndrome;
GFP=
green fluorescent protein;
HC=
healthy controls;
IgG=
immunoglobulin G;
MS=
multiple sclerosis;
NF=
neurofascin;
OCB=
oligoclonal immunoglobulin G bands;
OD=
optical density;
ON=
other neuropathies;
PNS=
peripheral nervous system;
ROC=
receiver operating characteristic

Footnotes

  • ↵* These authors contributed equally to this manuscript.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received December 30, 2012.
  • Accepted in final form May 6, 2013.
  • © 2013 American Academy of Neurology
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