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Abstract

Objective:

Previous histochemical studies in the demyelinating form of Guillain-Barré syndrome (GBS), acute inflammatory demyelinating polyneuropathy (AIDP), have shown complement deposition on the surface of Schwann cells, and therefore unknown epitopes would be present on the outer surface of Schwann cells.

Methods:

We used a proteomic-based approach to search for the target molecules of AIDP in the extracted proteins from schwannoma cells. Sera were obtained from 40 patients with GBS, 31 controls with inflammatory disease, and 46 normal controls.

Results:

We found that patients with AIDP after cytomegalovirus (CMV) infection have serum autoantibodies against membrane-organizing extension spike protein (moesin), which is expressed in the Schwann cell processes at the nodes of Ranvier and is crucial for myelination. Of the 40 patients with GBS, 6 had recent CMV infection and 5 of them (83%) had high levels of serum immunoglobulin G antibodies against moesin. The anti-moesin antibodies were found in none of the control subjects with disease including 5 with CMV infection but no neuropathy, and only 2 (4%) of the 46 normal control subjects. Immunocytochemistry showed that moesin was stained at the distal tips of schwannoma cells by sera from the patients with CMV-related AIDP but not by sera from controls.

Conclusion:

Moesin is a possible immunologic target molecule of pathogenic autoantibodies in patients with CMV-related AIDP.

Classification of evidence:

This study provides Class II evidence that levels of serum anti-moesin antibodies accurately distinguishes CMV-related AIDP from non–CMV-related AIDP (sensitivity 83%, specificity 93%).

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Supplementary Material

File (106.pdf)
File (figure_e-1.pdf)
File (sawai_113.pdf)

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Letters to the Editor
6 August 2014
Re:No evidence that molecular mimicry between cytomegalovirus and moesin causes AIDP
Setsu Sawai, Assistant Professor
Masahiro Mori, Chiba, Japan; Satoshi Kuwabara, Chiba, Japan

We appreciate Miyaji et al.'s further comments on our study. [1] As described in our paper, anti-moesin antibodies are also found in patients with the paroxysmal nocturnal hemoglobulinuria type of acquired aplastic anemia. [2] The anti-moesin antibodies in these 2 diseases recognize distinct epitopes of the moesin protein. The antibody in aplastic anemia was reported to recognize a C-terminal part of moesin amino acid sequences. [2] However, amino acid sequence 'HRGMLR', analyzed by the BLAST program by comparing the sequences of moesin and CMV proteins in our study, was located at a different site from the C- terminal, and was listed as the candidate of immune target. Separately, we completely agree that an animal model of AIDP by immunization with moesin protein (peptide) is necessary to confirm the disease pathogenesis of CMV-related AIDP, and we would like to do so in the future.

1. Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome. Neurology 2014;83:113-117.

2. Takamatsu H, Feng X, Chuhjo T, et al. Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia. Blood. 2007;109:2514-2520.

For disclosures, contact the editorial office at [email protected].

24 July 2014
No evidence that molecular mimicry between cytomegalovirus and moesin causes AIDP
Kazuki Miyaji, Research fellow
Nobuhiro Yuki, Singapore

We thank Dr. Sawai and colleagues for responding to our query. The presence of similar autoantibodies in aplastic anemia strongly suggests anti-moesin antibodies are unlikely to play a role in the development of Guillain-Barre syndrome. Sawai et al. described the amino acid sequences HRGMLR as common between cytomegalovirus and moesin. [1] To support the presence of molecular mimicry between cytomegalovirus and moesin, binding of patients' sera with the peptide HRGMLR should be demonstrated.

Previous studies demonstrated molecular mimicry between Campylobacter jejuni and GM1 or GD1a, and replicas of acute motor axonal motor neuropathy by active immunization of GM1 or passive transfer of anti-GM1 antibodies. [2-5] To prove the current hypothesis, it is important to produce an animal model of acute inflammatory demyelinating polyneuropathy by active immunization of the hexapeptides or passive transfer of the IgG antibodies to the peptides.

1. Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome. Neurology 2014;83:113-117.

2. Yuki N, Taki T, Inagaki F, et al. A bacterium lipopolysaccharide that elicits Guillain-Barre syndrome has a GM1 ganglioside-like structure. J Exp Med 1993;178:1771-1775.

3. Yuki N, Yamada M, Koga M, et al. Animal model of axonal Guillain-Barre syndrome induced by sensitization with GM1 ganglioside. Ann Neurol 2001;49:712-720.

4. Goodfellow JA, Bowes T, Sheikh K, et al. Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody-mediated injury in a model of acute motor axonal neuropathy. J Neurosci 2005;25:1620-1628.

5. Greenshields KN, Halstead SK, Zitman FMP, et al. The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice. J Clin Invest 2009;119:595-610.

For disclosures, please contact the editorial office at [email protected].

8 July 2014
Re:Is moesin a real target for AIDP?
Setsu Sawai, Assistant Professor
Masahiro Mori, Chiba, Japan; Satoshi Kuwabara, Chiba, Japan

Miyaji et al. stated that in their Guillain-Barre syndrome cohort, anti- moesin antibodies were not detected by enzyme-linked immunosorbent assay. Our report showed positive anti-moesin antibodies in patients with cytomegalovirus-related Guillain-Barre syndrome by immunoblotting and immunocytochemistry. For proper comparison, the same methods should be used to validate previously reported findings. Results of antibody assays may not be identical by different assays such as enzyme-linked immunosorbent assay, and future studies are required.

Miyaji et al. also mentioned that moesin is an intracellular protein and thereby an unlikely immunological target molecule. Moesin classically links the cell membrane and cytoskeleton, and mediates the formation of microtubules and cell adhesion sites. [1] Several studies have reported that moesin is also detected on the cell surface of lymphocytes and macrophages by flow cytometry, indicating that moesin regulates cytokine production when activated by infection or inflammation. [2-4] Moreover, anti-moesin antibodies are detected in sera from patients with aplastic anemia. [5] Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome, as we indicated in our title.

1. Tsukita S, Yonemura S. Cortical actin organization: lessons from ERM (ezrin/radixin/moesin) proteins. J Biol Chem 1999;274:34507-34510.

2. Amar S, Oyaisu K, Li L, et al. Moesin: a potential LPS receptor on human monocytes. J Endotoxin Res 2001;7:281-286.

3. Iontcheva I, Amar S, Zawawi KH, et al. Role for moesin in lipopolysaccharide-stimulated signal transduction. Infect Immun 2004;72:2312-2320.

4. Takamatsu H, Espinoza JL, Lu X, et al. Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma. J Immunol 2009;182:703-710.

5. Takamatsu H, Feng X, Chuhjo T, et al. Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia. Blood 2007;109:2514-2520.

For disclsoures, please contact the editorial office at [email protected].

27 June 2014
Is moesin a real target for AIDP?
Kazuki Miyaji, Research fellow
Jerome Devaux, Marseille, France; Nobuhiro Yuki, Singapore

Sawai et al. [1] reported moesin as a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome, especially acute inflammatory demyelinating polyneuropathy (AIDP). We aimed to validate their observations in our cohort of patients with AIDP by enzyme-linked immunosorbent assay, which usually has a higher sensitivity than immunoblotting. None of the 41 patients with AIDP, including 8 cytomegalovirus-related AIDP patients, had IgG or IgM antibodies to moesin (unpublished data).

Deposition of activated complement components and membrane attack complex were observed along the outer surface of Schwann cells in the motor nerves of AIDP patients. [2] This finding suggested that target molecules are extracellular. Moesin along with ezrin and radixin were present as intracellular proteins. We believe that moesin is an unlikely target molecule for cytomegalovirus-related AIDP.

1. Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome. Neurology 2014;83:113-117.

2. Hafer-Macko CE, Sheikh KA, Li CY, et al. Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Ann Neurol 1996;39:625-635.

For disclosures, please contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 83Number 2July 8, 2014
Pages: 113-117
PubMed: 24920858

Publication History

Received: September 10, 2013
Accepted: February 7, 2014
Published online: June 11, 2014
Published in print: July 8, 2014

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Disclosure

S. Sawai, M. Satoh, M. Mori, S. Misawa, K. Sogawa, T. Kazami, M. Ishibashi, M. Beppu, K. Shibuya, T. Ishige, Y. Sekiguchi, K. Noda, K. Sato, K. Matsushita, Y. Kodera, and F. Nomura report no disclosures relevant to the manuscript. S. Kuwabara serves as an editorial board member of the Journal of the Neurological Sciences, and as an associate editor of the Journal of Neurology, Neurosurgery, and Psychiatry. Go to Neurology.org for full disclosures.

Study Funding

Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (S.S., 23790976) and the Research Committee for Neuroimmunological Diseases of the Research on Measures for Intractable Diseases from the Ministry of Health, Welfare and Labour of Japan (S.K.).

Authors

Affiliations & Disclosures

Setsu Sawai, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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Mamoru Satoh, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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1.
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Masahiro Mori, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
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Sonoko Misawa, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Research Grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Kakenhi-21790834)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
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1.
NONE
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1.
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1.
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Kazuyuki Sogawa, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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Takahiro Kazami, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
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1.
NONE
Legal Proceedings:
1.
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Masumi Ishibashi
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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1.
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Minako Beppu, MD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
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1.
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Kazumoto Shibuya, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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Takayuki Ishige
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
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1.
NONE
Legal Proceedings:
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Yukari Sekiguchi, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kenta Noda, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kenichi Sato, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kazuyuki Matsushita, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Yoshio Kodera, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Fumio Nomura, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Satoshi Kuwabara, MD, PhD
From the Departments of Molecular Diagnosis (S.S., M.S., K. Sogawa, T.K., M.I., M.B., T.I., K.N., K. Sato, K.M., F.N.) and Neurology (M.M., S.M., M.B., K. Shibuya, Y.S., S.K.), Graduate School of Medicine, Chiba University; and Department of Physics (Y.K.), School of Science, Kitasato University, Kanagawa, Japan.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1)Associate Editor, Journal of Neurology, Neurosurgery, and Psychiatry, since 2010 to present. (2)Editorial board member, Journal of the Neurological Sciences, since 2013 to present.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Sawai: [email protected]
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.

Author Contributions

Drs. Sawai, Mori, and Kuwabara designed the study and drafted the manuscript. Drs. Misawa, Beppu, and Sekiguchi contributed the clinical data and serum samples. Drs. Sawai, Satoh, Sogawa, and Mr. Ishige performed proteomic analyses. Ms. Ishibashi, Drs. Noda and Sato measured the anti-moesin autoantibody in the serum samples. Drs. Kazami and Shibuya performed immunohistochemistry. Drs. Matsushita, Kodera, and Nomura supervised the experiments.

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