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March 2020; 7 (2) ArticleOpen Access

Intrathecal B-cell activation in LGI1 antibody encephalitis

Klaus Lehmann-Horn, Sarosh R. Irani, Shengzhi Wang, Arumugam Palanichamy, Sarah Jahn, Ariele L. Greenfield, Ravi Dandekar, Gildas Lepennetier, Sophia Michael, Jeffrey M. Gelfand, Michael D. Geschwind, Michael R. Wilson, Scott S. Zamvil, H.-Christian von Büdingen
First published February 6, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000669
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Article Information

vol. 7 no. 2 e669
DOI: 
https://doi.org/10.1212/NXI.0000000000000669
PubMed: 
32029531
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received September 5, 2019
  • Accepted in final form December 23, 2019
  • First Published February 6, 2020.
Copyright & Usage: 
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 License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Author Disclosures

    1. Klaus Lehmann-Horn, MD*,
    2. Sarosh R. Irani, MD, PhD*,
    3. Shengzhi Wang, PhD,
    4. Arumugam Palanichamy, PhD,
    5. Sarah Jahn,
    6. Ariele L. Greenfield, MD,
    7. Ravi Dandekar, MSc,
    8. Gildas Lepennetier, PhD,
    9. Sophia Michael,
    10. Jeffrey M. Gelfand, MD,
    11. Michael D. Geschwind, MD, PhD,
    12. Michael R. Wilson, MD,
    13. Scott S. Zamvil, MD, PhD and
    14. H.-Christian von Büdingen, MD
  1. Klaus Lehmann-Horn, MD*,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Novartis, speaker honorarium (2) F. Hoffmann-La Roche, speaker honorarium (3) Merck Serono, compensation for travel expenses

    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. (1) Oppenheim Award for Multiple Sclerosis Research 2015, sponsored by Novartis (2) Novartis, research support to TUM, unrelated to the study

    Research Support, Government Entities:

    1. Deutsche Forschungsgemeinschaft (German Research Foundation) (Le 3079/1-1) Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy) Deutsche Forschungsgemeinschaft (German Research Foundation) CRC TR128

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National Multiple Sclerosis Society (FG 2067-A-1) Hertie Foundation

    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. Sarosh R. Irani, MD, PhD*,
    3. Scientific Advisory Boards:

    1. Encephalitis Society (non-profit, charity). ADC therapeutics and UCB (commercial)

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. SRI has received honoraria for speaking at scientific conferences, including the Movement Disorder Society, Dublin Neuroimunology Symposium, Korean Encephalitis meeting and Bethel Epilepsy Symposium.

    Editorial Boards:

    1. NONE

    Patents:

    1. SRI receives royalties on patent application WO/2010/046716 entitled 'Neurological Autoimmune Disorders'. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. 1. Commercial. MedImmune Ltd. 2. ADCT 3. Minnetronix Neuro Inc 4. UCB Pharma 5. Medicolegal projects (various)

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Commercial: SRI has received research funding from UCB, CSL Behring and ONO pharmaceuticals

    Research Support, Government Entities:

    1. S.R.I has received a NIHR fellowship, Department of Health, UK to fund his DPhil/PhD

    Research Support, Academic Entities:

    1. SRI received funding support from a Wellcome Intermediate Clinical Fellowship, BMA Research Grants - Vera Down grant, the Fulbright UK- US commission and the MS society (2012-2013).

    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. For VGKC-complex antibody patent, as described above. Royalties paid by OUI, University of Oxford's IP company in 2012 and 2013.

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Shengzhi Wang, PhD,
    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

  4. Arumugam Palanichamy, 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. Current employee of Janssen Inc

    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. Sarah Jahn,
    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. Five Prime Therapeutics, senior scientific researcher, 3 years

    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. Ariele L. Greenfield, MD,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. "Apparatus and method for isolating single particles from a particle suspension"

    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. National Multiple Sclerosis Society

    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. Ravi Dandekar, MSc,
    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. (1) University of California, San Francisco

    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. Gildas Lepennetier, PhD,
    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. Sophia Michael,
    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. 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

  10. Jeffrey M. Gelfand, MD,
    11. Scientific Advisory Boards:

    1. DSMB for a National Institutes of Aging funded study.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Dr. Gelfand is on the editorial advisory board of Neurology Neuroimmunology & Neuroinflammation. Dr. Gelfand's wife is an associate editor for JAMA Neurology.

    Patents:

    1. NONE

    Publishing Royalties:

    1. Honoraria from Dynamed Plus for editorial review. Dr. Gelfand's spouse has received honoraria from UpToDate.

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Dr. Gelfand has received consulting fees from Biogen and Alexion. His spouse has received consulting fees from Theranica, Impel Neuropharma, Eli Lilly, Impax and Zosano; eNeura provides consulting payments for work done by Dr. Gelfand's spouse to the UCSF Pediatric Headache program.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Research support (to University of California, San Francisco) from Genentech; support from a service contract from MedDay. His spouse receives grant support from Amgen.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. PI of an Institutional Clinician Training Award from the National MS Society.

    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. Dr. Gelfand has received compensation for medical-legal consulting as an expert witness, and his spouse has also received personal compensation for medical- legal consulting as an expert witness.

  11. Michael D. Geschwind, MD, PhD,
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Speaking honorarium from Oakstone Publishing, Inc. and Wolters Kluwer Health/AudioDigest.

    Editorial Boards:

    1. Editorial board, "Dementia & Neuropsychologia" ∼2010- present

    Patents:

    1. NONE

    Publishing Royalties:

    1. Received one time payment from John C. Wiley for 2017 publication on prion disease.

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. serves or has served as a consultant Advanced Medical Inc., Best Doctors Inc., Grand Rounds Inc., Gerson Lehrman Group Inc, Guidepoint Global, Market Plus LLC, Trinity Partners LLC, and Quest Diagnostics. Consulting various medical-legal expert witness consulting for individual cases for Smith & Hennessey LLC, Anderson Boutwell Traylor LTD, Wallace & Millsap, LLC, and Maupin Cox Legoy LLC.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Quest Diagnostics, Inc.

    Research Support, Government Entities:

    1. Research support from NIH/NIA R01 AG031189 PI 2013-2019, R56 AG055619-01A 2018-2019, Alliance Biosecure 2016-18.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. 1. Michael J. Homer Family Fund 2. CurePSP 3. Tau Consortium

    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

  12. Michael R. Wilson, MD,
    13. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Merck, speaking honorarium

    Editorial Boards:

    1. NONE

    Patents:

    1. 1. Depletion of Abundant Sequences by Hybridization (DASH) 2. Method for High Percentage Recovery of Rare Cells 3. Autoantibodies as Biomarker of Paraneoplastic Encephalitis Associated with Testicular Cancer

    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. Roche/Genentech

    Research Support, Government Entities:

    1. 1. National Institute of Neurological Disorders and Stroke, K08 NS096117, PI, 2016-2021 2. National Institute of Allergy and Infectious Diseases, 1R01AI145437, PI, 2019-2024

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. 1. Sandler Foundation 2. William K. Bowes, Jr. Foundation 3. Rachleff Family Foundation 4. UCSF Weill Institute for Neurosciences 5. Marcus Foundation

    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. Scott S. Zamvil, MD, PhD and
    14. Scientific Advisory Boards:

    1. Dr. Zamvil has received honoraria for serving on Data Safety Monitoring Boards for MS trials conducted by Opexa, BioMS, Teva Pharmaceuticals, Inc. and Eli Lilly and Co. He is a member of the Clinical Advisory Board for the Myelin Repair Foundation.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Biogen - Speaker honoraria and advisory board meetings (2) Teva - Speaker honoraria and advisory board meetings

    Editorial Boards:

    1. (1) Neurology, Neuroimmunology and Neuroinflammation, Deputy Editor, 2014-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. SSZ has served as a consultant to Biogen Idec, Teva Neuroscience, EMD-Serono, Genzyme, Novartis and Roche.

    Speakers' Bureaus:

    1. Advanced Health Media, 2009-present Biogen, 2009-present

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Biogen - speaker and advisory board meetings (2) Teva - speaker and advisory board meetings (3) Genentech - advisory board meeting (4) Novartis - advisory board meetings (5) Genzyme - advisory board meetings (6) Alexion - advisory board meeting

    Research Support, Government Entities:

    1. NIH RO1 NS092835-01 NIH RO1 AI131624-O1A1 NIH R21 NS10815990-01

    Research Support, Academic Entities:

    1. NMSS RG 1701-26628 NMSS RG 1801-29861

    Research Support, Foundations and Societies:

    1. Alexander M. and June L. Maisin Foundation, PI

    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

  14. H.-Christian von Büdingen, MD
    15. Scientific Advisory Boards:

    1. (2) Novartis, Roche

    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. F. Hoffmann La-Roche, Basel, Switzerland, Medical Director, since 2016

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. F. Hoffmann-La Roche Ltd, Pfizer

    Research Support, Government Entities:

    1. NIH/NINDS, K02NS072288, PI, 2011-2016NIH/NINDS, 1R01NS092835, PI, 2015

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National Multiple Sclerosis SocietyRachleff Family Foundation

    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. F. Hoffmann-La Roche, 2016 to 2019

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Department of Neurology (K.L.-H., S.W., A.P., S.J., A.L.G., R.D., J.M.G., M.D.G., M.R.W., S.S.Z., H.-C.v.B.), UCSF Weill Institute for Neurosciences; Program in Immunology (K.L.-H., S.S.Z.), UCSF, San Francisco, CA; Department of Neurology (K.L.-H., G.L.), Klinikum rechts der Isar, Technische Universität München, Germany; and Oxford Autoimmune Neurology Group (S.R.I., S.M.), John Radcliffe Hospital, University of Oxford, UK.
  1. Correspondence
    Dr. Lehmann-Horn klaus.lehmann-horn{at}tum.de
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