Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

September 2021; 8 (5) ArticleOpen Access

Antiplexin D1 Antibodies Relate to Small Fiber Neuropathy and Induce Neuropathic Pain in Animals

Takayuki Fujii, View ORCID ProfileEun-Jae Lee, Yukino Miyachi, Ryo Yamasaki, Young-Min Lim, Kyoko Iinuma, Ayako Sakoda, Kwang-Kuk Kim, Jun-ichi Kira
First published June 7, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001028
Takayuki Fujii
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: takayuki@neuro.med.kyushu-u.ac.jp
Eun-Jae Lee
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Eun-Jae Lee
  • For correspondence: siverash@gmail.com
Yukino Miyachi
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ykno.m.223@gmail.com
Ryo Yamasaki
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ryoya@neuro.med.kyushu-u.ac.jp
Young-Min Lim
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: limy@amc.seoul.kr
Kyoko Iinuma
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kyoiinuma@gmail.com
Ayako Sakoda
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: sakoda-a@neuro.med.kyushu-u.ac.jp
Kwang-Kuk Kim
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kkim601@gmail.com
Jun-ichi Kira
From the Department of Neurology (T.F., Y.M., R.Y., K.I., A.S., J.-i.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (E.-J.L., Y.-M.L., K.-K.K.), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Translational Neuroscience Center (J.-i.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa; and Department of Neurology (J.-i.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Antiplexin D1 Antibodies Relate to Small Fiber Neuropathy and Induce Neuropathic Pain in Animals
Takayuki Fujii, Eun-Jae Lee, Yukino Miyachi, Ryo Yamasaki, Young-Min Lim, Kyoko Iinuma, Ayako Sakoda, Kwang-Kuk Kim, Jun-ichi Kira
Neurol Neuroimmunol Neuroinflamm Sep 2021, 8 (5) e1028; DOI: 10.1212/NXI.0000000000001028

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
792

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Article Figures & Data

Figures

  • Tables
  • Figure 1
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1 ELISA Screen and Confirmatory TBA for Plexin D1-IgG

    (A) Indirect ELISA for plexin D1-IgG in a previous cohort of 8 patients with NeP with plexin D1-IgG and 50 non-NeP patients (30 disease controls and 20 HCs) previously determined by TBA. Disease controls included 6 with amyotrophic lateral sclerosis; 4 each with multiple system atrophy, systemic lupus erythematosus, and neuro-Behçet disease; 3 with hereditary spinocerebellar degeneration; 2 each with Parkinson disease, normal pressure hydrocephalus, and Sjögren syndrome; and 1 each with Alzheimer disease, dementia with Lewy bodies, and corticobasal degeneration. The difference in OD values between plexin D1-coated wells and D1-uncoated wells (corrected OD value) was calculated, and the test was considered “ELISA-positive” when the corrected OD value was above the mean + 5 SD of the 50 plexin D1-IgG-negative controls determined by TBA (0.163, dotted line). Six of 8 patients with NeP with plexin D1-IgG by TBA were positive for plexin D1-IgG by ELISA, whereas all 50 disease controls and HCs without plexin D1-IgG by TBA were negative for plexin D1-IgG by ELISA. (B) Comparison of the newly established ELISA with TBA for plexin D1-IgG. The overall coincidence rate of ELISA to TBA was 96.6% (56/58). (C) Indirect ELISA for plexin D1-IgG in the present SFN cohort. The difference in OD values between plexin D1-coated wells and D1-uncoated wells (corrected OD value) was calculated, and the test was considered “ELISA-positive” when the corrected OD value was above 0.163 (dotted line). Plexin D1-IgG was positive in 8 of 63 (12.7%) of all patients with SFN, including 6 of 38 (15.8%) patients with iSFN, 2 of 25 (8.0%) patients with sSFN, and 2 of 55 (3.6%) HCs by ELISA. (D) IgG (green) from a representative patient with SFN (iSFN Case 1 in table 2) showed positive immunostaining of mouse small DRG neurons, whereas there was no significant immunoreactivity in 2 ELISA-seropositive HCs (HC 1 and HC 2). Nuclei are counterstained with 4′,6-diamidino-2-phenylindole (DAPI) (blue). (E) Correlation between the corrected OD value and the disease duration in patients with SFN with plexin D1-IgG (n = 8). There was a significant positive correlation between them (Spearman rank correlation; rs = 0.9639, p = 0.0001). Even after 1 outlier with the highest optical density was removed, the correlation between the corrected OD value and the disease duration remained significant (rs = 0.982, p < 0.0001). HC = healthy control; IgG = immunoglobulin G; iSFN = idiopathic small fiber neuropathy; OD = optical density; SFN = small fiber neuropathy; sSFN = secondary small fiber neuropathy; TBA = tissue-based indirect immunofluorescence assay.

  • Figure 2
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2 Assessment of Pain-Like Behaviors and Neuronal Activation in Passive Transfer Mice 24 Hours After Injection

    (A) Mechanical pain hypersensitivity was assessed by calibrated von Frey filaments (0.04, 0.07, 0.16, 0.40, and 0.60 g) 24 hours after injection. Mice treated with purified IgG from patients 1, 2, and 3 showed significantly higher reaction rates to each stimulation strength (0.07, 0.16, 0.40, and 0.60 g filaments) than HC IgG-treated mice (1-way ANOVA with Dunnett test; *p < 0.01). No significant differences in reaction rates were seen with IgG from 2 inflammatory disease controls (1 patient with NBD and 1 patient with NPSLE) and patients 1, 2, and 3 after preadsorption with rhPlexin D1 compared with control IgG (1-way ANOVA with Dunnett test). (B) Indirect IFA of mouse L5 DRG sections revealed that IgG (green) from the patient with SFN (patient 3) with plexin D1-IgG but not control IgG bound to small DRG neurons. IgG from patient 3 preabsorbed with rhPlexin D1 (2 µg/mL) showed no significant immunoreactivity to mouse DRG. Nuclei are counterstained with 4′,6-diamidino-2-phenylindole (blue). Immunostaining of pERK, a marker of primary afferent neuron activation, in L5 DRG of mice treated with purified IgG from patient 3 and control 24 hours after injection. Most of the pERK-labeled neurons in mice treated with purified IgG from patient 3 are small DRG neurons (≤25 µm in diameter). Few neurons are labeled for pERK in mice treated with control IgG and IgG from patient 3 after preabsorption with rhPlexin D1. Sections were counterstained with hematoxylin. (C) Distribution of pERK immunoreactivity among different-sized neurons was analyzed. DRG neurons were stratified as small (≤25 mm in diameter) and large (>25 mm in diameter) neurons. The pERK-labeled neurons in L5 DRG of mice treated with purified IgG from patients 1, 2, and 3 were predominantly small neurons of less than 25 μm in diameter. Scale bars = 50 µm and (inset) = 25 µm. ANOVA = analysis of variance; DRG = dorsal root ganglia; HC = healthy control; IFA = immunofluorescence assay; IgG = immunoglobulin G; NBD = neuro-Behçet disease; NPSLE = neuropsychiatric systemic lupus erythematosus; pERK = phosphorylated extracellular signal-regulated protein kinase; Pre-Ab = preabsorbed; rhPlexin D1 = recombinant human plexin D1.

Tables

  • Figures
  • Table 1
  • Table 2
  • Table 3
  • Table
  • links.lww.com/NXI/A497
  • links.lww.com/NXI/A495
  • links.lww.com/NXI/A496

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study Funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Preferences and User Experiences of Wearable Devices in Epilepsy A Systematic Review and Mixed-Methods Synthesis

Dr. Daniel Friedman and Dr. Sharon Chiang

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Autoimmune diseases
  • Neuropathic pain
  • Peripheral neuropathy

Alert Me

  • Alert me when eletters are published
Neurology - Neuroimmunology Neuroinflammation: 10 (2)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise