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November 2019; 6 (6) ArticleOpen Access

HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease

Carles Gaig, Guadalupe Ercilla, Xavier Daura, Mario Ezquerra, Ruben Fernández-Santiago, Eduard Palou, Lidia Sabater, Romana Höftberger, Anna Heidbreder, Birgit Högl, Alex Iranzo, Joan Santamaria, Josep Dalmau, Francesc Graus
First published August 12, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000605
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Article Information

vol. 6 no. 6 e605
DOI: 
https://doi.org/10.1212/NXI.0000000000000605
PubMed: 
31454761
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received April 4, 2019
  • Accepted in final form July 1, 2019
  • First Published August 12, 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. Carles Gaig, MD, PhD,
    2. Guadalupe Ercilla, MD, PhD,
    3. Xavier Daura, PhD,
    4. Mario Ezquerra, PhD,
    5. Ruben Fernández-Santiago, PhD,
    6. Eduard Palou, MD, PhD,
    7. Lidia Sabater, PhD,
    8. Romana Höftberger, MD,
    9. Anna Heidbreder, MD, PhD,
    10. Birgit Högl, MD, PhD,
    11. Alex Iranzo, MD, PhD,
    12. Joan Santamaria, MD, PhD,
    13. Josep Dalmau, MD, PhD and
    14. Francesc Graus, MD, PhD
  1. Carles Gaig, 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. Guadalupe Ercilla, MD, 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. 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. Xavier Daura, 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. Mario Ezquerra, PhD,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. Patent Ref. Nr. UBTT304: ?Method for predicting L-DOPA induced dyskinesia onset and severity?. Inventors: M. J. Mart?, Dr. M. Ezquerra, Dr. R. Fern?ndez-Santiago. Invention: method for predicting the L-DOPA induced dyskinesia (LID) onset and severity in patients with Parkinson?s disease (PD) treated with this compound. Current stage of development: Priority patent application filed.

    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. MicroRNAs as biomarkers of the prodromal stage of Parkinson disease. Funding entity: The Michael J Fox Foundation for Parkinson?s Disease Research (MJFF). Amount: 210.791$. From: 2016 To: 2019 Co-Principal investigator: Mario Ezquerra (co-PI). MicroRNAs como biomarcadores de conversi?n de trastorno conductual de sue?o REM a enfermedad de Parkinson Funding entity: Fundacion Tatiana Guzman El Bueno. Amount: 77.000 euros. From: 2017 To: 2019. Principal investigator: Mario Ezquerra.

    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. Ruben Fernández-Santiago, 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. 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. I, R.F.-S., was supported by a J?venes Investigadores (JIN) grant of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Agencia Estatal de Investigaci?n (AEI) (AEI/FEDER/UE) (grant # SAF2015-73508-JIN) (2016-2019).

    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. Eduard Palou, MD, PhD,
    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. (1)Spanish government/Carlos III Health Institute, PI17/00078, Co-principal investigator, 2018-2020

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. (1) Foundation of the Academy of Medical and Health Sciences from Catalonia

    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. Lidia Sabater, 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. Romana Höftberger, MD,
    9. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. speaker honoraria from Euroimmun

    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. Anna Heidbreder, MD, PhD,
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. speaker honoraria for UCB, Bioprojet, Servier, Medice

    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. Birgit Högl, MD, PhD,
    11. Scientific Advisory Boards:

    1. 1. Axovant2. Benevolent Bio3. Roche4. Takeda

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. speaker honorarium or travel support: (1) Habel Medizintechnik, Vienna, Austria(2) Novartis(3) AoP Orphan(4) Inspire

    Editorial Boards:

    1. (1) J Clin Sleep Med;(2) Sleep Medicine;(3) Somnologieall without compensation

    Patents:

    1. NONE

    Publishing Royalties:

    1. Disorders of Sleep and Circadian Rhythms in Parkinson?s disease. Springer, 2015REM Sleep Behavior Disorder. Srpinger, 2018

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Mundipharma, UCB, Axovant, Benevolent Bio

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. Travel Support Habel Medizintechnik and Vivisol Austria

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. UCB

    Research Support, Government Entities:

    1. FWF Austrian Science Funds I2120 B27, PI, 2015-2018FWF Austrian Science Funds, KLI633

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Government of Tyrol, no number, PI, 2012-2016

    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. Alex Iranzo, MD, PhD,
    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

  12. Joan Santamaria, MD, PhD,
    13. 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. Grant from Fundaci? La Marat? TV3, Catalonia, Spain; 2015 to now

    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. Josep Dalmau, MD, PhD and
    14. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Neurology, Neuroimmunology and Neuroinflammation Neurology UpToDate

    Patents:

    1. Patent for Ma2 autoantibody test: US 6,387,639; Issued May 14th, 2002. Patent for NMDA receptor autoantibody test: US 7,972,796 B2 July 5, 2011; European 2057466. Patent for GABAb receptor autoantibody test: US 8,685,656; European 2483417; Patents filed for GABA(A) receptor autoantibody test, DPPX autoantibody test, and IgLON5 autoantibody test.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Advance Medical

    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, RO1NS077851, PI, 2011-2018 -Instituto Carlos III/FEDER (FIS, 14/00203 and CIBERER CB15/00010, and Proyectos Integrados de Excelencia, PIE 16/00014). -Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), and CERCA Programme Generalitat de Catalunya -ERA-NET Neuron

    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. NMDA receptor autoantibody test/Euroimmun GABA(B)R autoantibody test/Euroimmun GABA(A)R autoantibody test/Euroimmun DPPX autoantibody test/Euroimmun Iglon5 autoantibody test/Euroimmun

    Royalty Payments, Technology or Inventions:

    1. Patent Ma2 autoantibody test Patent NMDAR autoantibody test Patent GABA(B) receptor autoantibody test Patent application for the use of GABA(A) receptor, DPPX and IgLON5 autoantiboddy tests

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  14. Francesc Graus, MD, PhD
    15. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. member of the editorial Board of Lancet neurology since 2002

    Patents:

    1. use of IgLON5 as a diagnostic test.

    Publishing Royalties:

    1. Dr. Graus receives royalties from licensing fees to Euroimmun for the use of IgLON5 as a diagnostic test.

    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

  1. From the Service of Neurology (C.G., A.I., J.S.), Hospital Clinic, Barcelona, Spain; Multidisciplinary Sleep Disorders Unit (C.G., A.I., J.S.), Hospital Clinic, Barcelona, Spain; Department of Immunology (G.E., E.P.), Hospital Clínic, Barcelona, Spain; Institute of Biotechnology and Biomedicine (X.D.), Universitat Autònoma de Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA) (X.D., J.D.), Barcelona, Spain; Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders (M.E., R.F.-S.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology Program (L.S., J.D., F.G.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Institute of Neurology (R.H.), Medical University of Vienna, Austria; Institute for Sleep Medicine and Neuromuscular Disorders (A.H.), University Hospital Muenster, Muenster, Germany; Department of Neurology (B.H.), Medical University of Innsbruck, Innsbruck, Austria; and Department of Neurology (J.D.), University of Pennsylvania, Philadelphia, PA.
  1. Correspondence
    Dr. Gaig cgaig{at}clinic.ub.es
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