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May 2019; 6 (3) ArticleOpen Access

MuSK myasthenia gravis monoclonal antibodies

Valency dictates pathogenicity

Maartje G. Huijbers, Dana L. Vergoossen, Yvonne E. Fillié-Grijpma, Inge E. van Es, Marvyn T. Koning, Linda M. Slot, Hendrik Veelken, Jaap J. Plomp, Silvère M. van der Maarel, Jan J. Verschuuren
First published February 21, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000547
Maartje G. Huijbers
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
PhD
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Dana L. Vergoossen
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
MSc
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Yvonne E. Fillié-Grijpma
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
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Inge E. van Es
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
BASc
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Marvyn T. Koning
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
BSc
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Linda M. Slot
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
MSc
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Hendrik Veelken
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
MD, PhD
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Jaap J. Plomp
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
PhD
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Silvère M. van der Maarel
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
PhD
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Jan J. Verschuuren
From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
MD, PhD
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Full PDF
Citation
MuSK myasthenia gravis monoclonal antibodies
Valency dictates pathogenicity
Maartje G. Huijbers, Dana L. Vergoossen, Yvonne E. Fillié-Grijpma, Inge E. van Es, Marvyn T. Koning, Linda M. Slot, Hendrik Veelken, Jaap J. Plomp, Silvère M. van der Maarel, Jan J. Verschuuren
Neurol Neuroimmunol Neuroinflamm May 2019, 6 (3) e547; DOI: 10.1212/NXI.0000000000000547

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Article Information

vol. 6 no. 3 e547
DOI: 
https://doi.org/10.1212/NXI.0000000000000547
PubMed: 
30882021

Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received December 3, 2018
  • Accepted in final form January 14, 2019
  • First Published February 21, 2019.

Copyright & Usage: 
Copyright © 2019 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.

Author Disclosures

    1. Maartje G. Huijbers, PhD,
    2. Dana L. Vergoossen, MSc,
    3. Yvonne E. Fillié-Grijpma,
    4. Inge E. van Es, BASc,
    5. Marvyn T. Koning, BSc,
    6. Linda M. Slot, MSc,
    7. Hendrik Veelken, MD, PhD,
    8. Jaap J. Plomp, PhD,
    9. Silvère M. van der Maarel, PhD* and
    10. Jan J. Verschuuren, MD, PhD*
  1. Maartje G. Huijbers, PhD,
  2. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. NONE

    Editorial Boards:
    1. NONE

    Patents:
    1. I am co-inventor on several patent applications related to MuSK MG pathogenesis.

    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

  3. Dana L. Vergoossen, MSc,
  4. 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

  5. Yvonne E. Fillié-Grijpma,
  6. 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

  7. Inge E. van Es, BASc,
  8. 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

  9. Marvyn T. Koning, BSc,
  10. 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. Professor Steenhuis Fund

    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

  11. Linda M. Slot, MSc,
  12. 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

  13. Hendrik Veelken, MD, PhD,
  14. 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

  15. Jaap J. Plomp, PhD,
  16. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. NONE

    Editorial Boards:
    1. NONE

    Patents:
    1. Two patents pending on the pathomechanisms of MuSK MG antibodies

    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

  17. Silvère M. van der Maarel, PhD* and
  18. Scientific Advisory Boards:
    1. Prinses Beatrix Spierfonds, non-profit CORT, non-profit MRC Centre for Neuromuscular Diseases, non-profit Dutch CAA foundation, non-profit Spierziekten Centrum Nederland, non-profit

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. NONE

    Editorial Boards:
    1. Neuromuscular Disorders, editorial board, ongoing

    Patents:
    1. SMvdM is coinventor on several patent applications relatedto FSHD and to MuSK MG

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. GenomeScan, non-executive board member

    Consultancies:
    1. Fulcrum Therapeutics

    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

  19. Jan J. Verschuuren, MD, PhD*
  20. Scientific Advisory Boards:
    1. Myasthenia Foundation of America (MGFA) medical/scientific advisory board

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. NONE

    Editorial Boards:
    1. Journal of Neuromuscular Diseases, member editorial board, 2014-now

    Patents:
    1. Patents on MuSK myasthenia gravis

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. The Neurology department of the LUMC has received fees from Alexion, Argen-X, and Rapharma because of consultancies

    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. Princes Beatrix Spierfonds, grant for MG research, Prinicpal investigator.

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. Development of MuSK diagnostic antibody test for TECAN/IBL. Yearly payments to the LUMC

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  1. From the Department of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
  1. Correspondence
    Dr. Huijbers M.G.M.Huijbers{at}lumc.nl
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