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

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit 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

July 2020; 7 (4) EditorialOpen Access

Are aquaporin antibody titers useful outcome measures for neuromyelitis optica spectrum disorders?

View ORCID ProfileMarkus Reindl
First published May 28, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000759
Markus Reindl
From the Clinical Department of Neurology, Medical University of Innsbruck, Austria.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Markus Reindl
Full PDF
Citation
Are aquaporin antibody titers useful outcome measures for neuromyelitis optica spectrum disorders?
Markus Reindl
Neurol Neuroimmunol Neuroinflamm Jul 2020, 7 (4) e759; DOI: 10.1212/NXI.0000000000000759

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
675

Share

  • Article
  • Info & Disclosures
Loading

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory demyelinating disease of the CNS, characterized by an increased risk for severe relapses.1 Most patients with NMOSD (>70%) are seropositive for pathogenic antibodies against the aquaporin-4 (AQP4-Ab) water channel. Recently, several randomized controlled trials have demonstrated clinical effectiveness of immunosuppressive agents in AQP4-Ab positive NMOSD.2 However, a potential biomarker of NMOSD activity that could be measured serially and predicted relapses would assist clinicians in their selection of patients for immunotherapies. A few small observational studies have suggested changes in AQP4-Ab titers as a potential biomarker of NMOSD activity.3,4

In this issue of Neurology® Neuroimmunology & Neuroinflammation, Jitprapaikulsan et al.5 provided Class II evidence that neither AQP4-Ab titers nor complement-mediated cell killing has any significant prognostic or predictive utility in NMOSD. The authors have analyzed 336 serial serum samples from 82 AQP4-Ab seropositive patients taken preattack, at attack onset, or at remission. AQP4-Ab titers were not significantly changed between the preattack, attack, or remission samples or in those of individual patients during their disease course. Furthermore, maintenance immunotherapy did not significantly affect AQP4-Ab titers. Similarly, the ability of AQP4-Ab for complement-mediated killing in vitro was not influenced by disease activity or treatment. Differences to previous reports reporting conflicting results could be explained by the substantially larger number of patients and samples in this study.

However, the current study of Jitprapaikulsan et al. also had a number of potential limitations, such as its retrospective design, with samples having been collected many years before study (3–14 years), the effect of acute attack immunotherapies given before collection of attack sera, and the experimental setup using 10-fold dilution for titrations.

Previous studies on the utility of serum levels of autoantibodies in other neurologic autoimmune diseases have shown differential results. In myasthenia gravis, serum titers of acetylcholine receptor antibodies generally vary widely between patients and do not predict disease severity.6 By contrast, CSF and, to a lesser degree, serum antibody titers against the NMDA receptor have been associated with a poor outcome in NMDA receptor encephalitis.7 There is also conflicting evidence regarding the usefulness of serum antibody titers against the myelin oligodendrocyte glycoprotein (MOG-Ab) which are also present in a subset of AQP4-Ab seronegative NMOSD patients. Some studies have indicated that the clinical recovery or a monophasic disease course is associated with transient MOG-Ab titers, whereas other studies have not been able to confirm these findings.8 To summarize, there is controversial evidence about the value of serial serum antibody titers for monitoring disease activity in neurologic autoimmune diseases, which also applies to various other autoantibodies. Possible explanations for these disappointing findings are as follows: first, the limited ability of peripheral blood antibody levels to reflect the situation in the target organ (e.g., the CNS); second, pathogenic autoantibodies are known to be bound to their target antigens and may therefore not be detectable in the periphery; and finally, in autoimmune encephalitis, CSF autoantibodies levels could be of higher clinical relevance than those found in the serum.7,9

Therefore, distinct peripheral blood biomarkers such as neurofilament-light or glial fibrillary acid protein are urgently needed and currently under investigation for their prognostic role and their use as therapeutic biomarkers in NMOSD.10

Study funding

No targeted funding reported.

Disclosure

M. Reindl is supported by a research grant from the Austrian Science Fund (FWF, project P32699). The University Hospital and Medical University of Innsbruck (Austria; employer of M.R.) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany). Go to Neurology.org/NN for full disclosures.

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • See page e727

  • Received April 8, 2020.
  • Accepted in final form April 17, 2020.
  • Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

References

  1. 1.↵
    1. Wingerchuk DM,
    2. Banwell B,
    3. Bennett JL, et al
    . International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177–189.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Hartung HP,
    2. Aktas O
    . Old and new breakthroughs in neuromyelitis optica. Lancet Neurol 2020;19:280–281.
    OpenUrl
  3. 3.↵
    1. Takahashi T,
    2. Fujihara K,
    3. Nakashima I, et al
    . Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007;130:1224–1234.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Jarius S,
    2. Aboul-Enein F,
    3. Waters P, et al
    . Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 2008;131:3072–3080.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Jitprapaikulsan J,
    2. Fryer J,
    3. Majed M, et al
    . Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD. Neurol Neuroimmunol Neuroinflamm 2020;7:e727. doi: 10.1212/NXI.0000000000000727.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Lindstrom JM,
    2. Seybold ME,
    3. Lennon VA,
    4. Whittingham S,
    5. Duane DD
    . Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976;26:1054–1059.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Gresa-Arribas N,
    2. Titulaer MJ,
    3. Torrents A, et al
    . Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 2014;13:167–177.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Reindl M,
    2. Waters P
    . Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol 2019;15:89–102.
    OpenUrlPubMed
  9. 9.↵
    1. Graus F,
    2. Titulaer MJ,
    3. Balu R, et al
    . A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Watanabe M,
    2. Nakamura Y,
    3. Michalak Z, et al
    . Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD. Neurology 2019;93:e1299–e1311.
    OpenUrl

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

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. [email protected]
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
    • Study funding
    • Disclosure
    • Footnotes
    • References
  • Info & Disclosures
Advertisement

Hastening the Diagnosis of Amyotrophic Lateral Sclerosis

Dr. Brian Callaghan and Dr. Kellen Quigg

► Watch

Related Articles

  • Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Article
    Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders
    Douglas Kazutoshi Sato, Dagoberto Callegaro, Marco Aurelio Lana-Peixoto et al.
    Neurology, January 10, 2014
  • Article
    Fulminant demyelinating encephalomyelitis
    Insights from antibody studies and neuropathology
    Franziska Di Pauli, Romana Höftberger, Markus Reindl et al.
    Neurology - Neuroimmunology Neuroinflammation, November 04, 2015
  • Article
    Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD
    Jiraporn Jitprapaikulsan, James P. Fryer, Masoud Majed et al.
    Neurology: Neuroimmunology & Neuroinflammation, May 28, 2020
  • Article
    Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis
    Sudarshini Ramanathan, Stephen W. Reddel, Andrew Henderson et al.
    Neurology - Neuroimmunology Neuroinflammation, October 29, 2014
Neurology - Neuroimmunology Neuroinflammation: 11 (1)

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
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise