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January 2017; 4 (1) ArticleOpen Access

Effects of neuromyelitis optica–IgG at the blood–brain barrier in vitro

Yukio Takeshita, Birgit Obermeier, Anne C. Cotleur, Simona F. Spampinato, Fumitaka Shimizu, Erin Yamamoto, Yasuteru Sano, Thomas J. Kryzer, Vanda A. Lennon, Takashi Kanda, Richard M. Ransohoff
First published December 19, 2016, DOI: https://doi.org/10.1212/NXI.0000000000000311
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Article Information

vol. 4 no. 1 e311
DOI: 
https://doi.org/10.1212/NXI.0000000000000311
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received August 6, 2016
  • Accepted in final form November 2, 2016
  • First Published December 19, 2016.
Copyright & Usage: 
Copyright © 2016 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. Yukio Takeshita, MD, PhD,
    2. Birgit Obermeier, PhD,
    3. Anne C. Cotleur, MS,
    4. Simona F. Spampinato, MD, PhD,
    5. Fumitaka Shimizu, MD, PhD,
    6. Erin Yamamoto, BA,
    7. Yasuteru Sano, MD, PhD,
    8. Thomas J. Kryzer, AS,
    9. Vanda A. Lennon, MD,
    10. Takashi Kanda, MD, PhD and
    11. Richard M. Ransohoff, MD
  1. Yukio Takeshita, MD, PhD,
    2. 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

  2. Birgit Obermeier, PhD,
    3. 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. I am now employee of Biogen (Postdoctoral Scientist, for 2 years), but was affiliated with the Cleveland Clinic at the time the study was performed and I have no conflicts to declare.

    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. Anne C. Cotleur, MS,
    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. 1. Biogen, Senior Supervisor, 2years

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. 1. Employee at Biogen Nov 2014-present (myself)

    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

  4. Simona F. Spampinato, MD, PhD,
    5. 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. Fumitaka Shimizu, MD, PhD,
    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. Biogen, postdoctoral scientist, 1 years 10 month(2014.11- 2016.8)

    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

  6. Erin Yamamoto, BA,
    7. 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. Yasuteru Sano, MD, PhD,
    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

  8. Thomas J. Kryzer, AS,
    9. 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. Vanda A. Lennon, MD,
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. Vanda Lennon receives royalties from RSR/Kronus for sale of aquaporin-4 autoantibody testing kits and for commercial aquaporin-4 autoantibody testing performed outside Mayo Clinic.

    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. NIH R01-NS065829,?CNS Demyelinating Autoimmunity Targeting Water Channel Complexes?. Principal Investigator: S.J. Pittock Co-Investigator: V.A. Lennon Years: 2010-2015

    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. 1) RSR/Kronus for sale of aquaporin-4 autoantibody testing kits. 2) Non-Mayo sites performing “home brew” diagnostic testing for aquaporin-4 autoantibody.

    Royalty Payments, Technology or Inventions:

    1. Dr. Lennon has a potential financial interest in the technologies listed below: “Aquaporin-4 as an aid for cancer diagnosis”.

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Takashi Kanda, MD, PhD and
    11. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Clinical and Experimental Neuroimmunology Editor-in- Chief 2010- Neuropathology, Editorial Advisory Board Member 2009-

    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. Contract Grant Sponsor: Japan Society for the Promotion of Science - Tokyo Contract Grant Number: 25293203, 26670443

    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

  11. Richard M. Ransohoff, MD
    12. Scientific Advisory Boards:

    1. Chemocentryx

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. BiogenIdec, speaker's honoraria Novartis, speaker's honoraria

    Editorial Boards:

    1. Neurology; N2

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Employed at present by Biogen. Work reported in this paper was completed before I joined Biogen.

    Consultancies:

    1. Pfizer Teva

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Chemocentryx, sponsored research agreement Biogen, sponsored research agreement National MS Society

    Research Support, Government Entities:

    1. NIH: P50 NS38667 R01 NS32151 R01 NS74804 R21 NS74820 K24 NS51400

    Research Support, Academic Entities:

    1. Travel support and/or honoraria were provided for each of the following: Special Guest & Speaker Max-Planck Institute Retreat Ringberg Germany, 2009 Invited Plenary Speaker 1st Keystone Symposium on MS, Santa Fe New Mexico, 2009 Grand Rounds in Neurology, Johns Hopkins University, Baltimore, 2009 Keynote Lecture, Opening of Neuropathology Institute, Freiburg Germany, 2009 Plenary Lecture, Kick-off meeting for Neurodegeneration Research Center, Bonn, 2009 Invited Seminar, Institute for Research in Biomedicine, Bellinzona, Switzerland, 2009 Invited Speaker, FDA/NYAS Conference: ?Cytokine Therapies?, New York, 2009 Invited External Speaker ?Annual Japanese MS Workshop? Kyushu Japan 2009 Visiting Professor, Dept of Neurology, Kyushu University, Fukuoka, Japan, 2009 Consultant, Nature ?Landscape? editorial meeting on Neuroimmunology, 2009 Invited Seminar, GSK Hammersmith Hospital, London, 2009 Invited Speaker 12th International Symposium “Signaling at the BBB”, London, England, 2009 Co-organizer/Speaker ?Chemokines and Chemokine Receptors in the CNS?, Rome, 2009 Grand Rounds in Neurology, Ottawa General Hospital, Ontario, Canada, 2009 Invited Speaker, Keystone Symposium ?Alzheimer?s Disease?, Colorado, 2010 NIH EUREKA Review IRGs, 2008-2010 Invited Speaker, ASN annual meeting, Santa Fe, 2010 Invited Speaker, Nikolas Histiocytosis-X Symposium, Athens, Greece, 2010 Invited speaker, FOCIS 2010 Symposium ?Interventional Immunology?, Boston, 2010 Keynote Speaker, Neuroimmunology Symposium, Kyoto, Japan, 2010 Workshop Chair, International Congress of Immunology, Kobe, Japan 2010 Plenary Lecture, PACTRIMS, Bali, Indonesia, 2010 Symposium Organizer and Chair ANA annual meeting, San Francisco, CA, 2010 Workshop Chair, Special Interest Groups, ANA, San Francisco, CA, 2010 Invited Speaker, Theodor Kocher Institute, Bern, Switzerland, 2010 Invited Speaker/Session Chair, Cell Press Symposium “Inflammation in Disease”, Lisbon, 2010 Invited Speaker, Brazilian Society of Pharmacology 42nd Annual Meeting, Brazil, 2010 External Reviewer, DFG ?Centers of Excellence? Applications, Frankfurt, Germany, 2011 Invited Speaker, AAAS/Abelson Symposium ?Defeating AD?, Washington DC, 2011

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. SAB, Chemocentryx Employee, Biogen

    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

  1. From the Neuroinflammation Research Center (Y.T., B.O., A.C.C., S.F.S., F.S., E.Y., R.M.R.), Lerner Research Institute, Cleveland Clinic, OH; Department of Neurology and Clinical Neuroscience (Y.S., T.K.), Yamaguchi University Graduate School of Medicine, Japan; and Department of Laboratory Medicine and Pathology (T.J.K., V.A.L.), Mayo Clinic, Rochester, MN. Y.T. and F.S. are currently affiliated with the Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Japan. B.O., A.C.C., and R.M.R. are currently affiliated with Neuroimmunology Research, Biogen, Cambridge, MA. S.F.S. is currently affiliated with the Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Italy.
  1. Correspondence to Dr. Ransohoff: richard.ransohoff{at}biogen.com
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