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November 2021; 8 (6) ArticleOpen Access

Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis

Belinda Carrión, Yawei Liu, Mahdieh Hadi, Jon Lundstrom, Jeppe Romme Christensen, Cecilie Ammitzbøll, Morten Hanefeld Dziegiel, Per Soelberg Sørensen, Manuel Comabella, Xavier Montalban, Finn Sellebjerg, Shohreh Issazadeh-Navikas
First published August 12, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001065
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Article Information

vol. 8 no. 6 e1065
DOI: 
https://doi.org/10.1212/NXI.0000000000001065
PubMed: 
34385365
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received February 4, 2021
  • Accepted in final form June 16, 2021
  • First Published August 12, 2021.
Copyright & Usage: 
Copyright © 2021 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. Belinda Carrión, MD, PhD (bca{at}tec.mx),
    2. Yawei Liu, MD, PhD (yawei.liu{at}bric.ku.dk),
    3. Mahdieh Hadi, PhD (mahdieh.hadi{at}bric.ku.dk),
    4. Jon Lundstrom, MSc (jon.lundstrom{at}bric.ku.dk),
    5. Jeppe Romme Christensen, MD, PhD (jeppe.romme.christensen{at}regionh.dk),
    6. Cecilie Ammitzbøll, MD, PhD (cecilie.ammitzboell{at}regionh.dk),
    7. Morten Hanefeld Dziegiel, MD, PhD (morten.dziegiel{at}regionh.dk),
    8. Per Soelberg Sørensen, MD (per.soelberg.soerensen{at}regionh.dk),
    9. Manuel Comabella, MD, PhD (manuel.comabella{at}vhir.org),
    10. Xavier Montalban, MD, PhD (xavier.montalban{at}cem-cat.org),
    11. Finn Sellebjerg, MD, PhD (sellebjerg{at}dadlnet.dk) and
    12. Shohreh Issazadeh-Navikas, PhD
  1. Belinda Carrión, MD, PhD (bca{at}tec.mx),
    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. Yawei Liu, MD, PhD (yawei.liu{at}bric.ku.dk),
    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. Mahdieh Hadi, PhD (mahdieh.hadi{at}bric.ku.dk),
    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. MS International Federation-McDonald Fellowship to Mahdieh Hadi for two years. 2015

    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. Jon Lundstrom, MSc (jon.lundstrom{at}bric.ku.dk),
    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. Jeppe Romme Christensen, MD, PhD (jeppe.romme.christensen{at}regionh.dk),
    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

  6. Cecilie Ammitzbøll, MD, PhD (cecilie.ammitzboell{at}regionh.dk),
    7. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Genzyme, travel support

    Editorial Boards:

    1. NONE

    Patents:

    1. A patent pending for a stoma care invention. It is a device for collection of stoma output and it is a total different topic than this manuscript covers.

    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. Morten Hanefeld Dziegiel, MD, PhD (morten.dziegiel{at}regionh.dk),
    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. Per Soelberg Sørensen, MD (per.soelberg.soerensen{at}regionh.dk),
    9. Scientific Advisory Boards:

    1. (1) Merck KGaA (2) Teva(3) Novartis

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Merck KGaA: Travel and speaker honoraria for meetings, honoraria for serving on Independent Data Monitoring Committee(2) TEVA: Travel and speaker honoraria for meeting, educational activities.(5) Novartis: Travel and speaker honoraria for meeting, honoraria for serving on Independent Data Monitoring Committee

    Editorial Boards:

    1. (1) Therapeutic Advances in Neurological Diseases: Memberof External Editorial Board

    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. Manuel Comabella, MD, PhD (manuel.comabella{at}vhir.org),
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. I received speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.

    Editorial Boards:

    1. (1)Journal of Neuroimmunology, Editorial advisory board, (2009-present) (2)Multiple Sclerosis Journal, Editorial advisory board, (2013-present) (3)PLoS ONE, Editorial advisory board, (2014-2016)

    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)Red Española de Esclerosis Múltiple (REEM) 2014 - present. (2) Fondo de Investigación Sanitaria (FIS, Instituto de Salud Carlos III (2014 - present)

    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. Xavier Montalban, MD, PhD (xavier.montalban{at}cem-cat.org),
    11. Scientific Advisory Boards:

    1. (1) Actelion, (2) Alexion, (3) Biogen, (4) Bristol-Myers Squibb/Celgene, (5) EMD Serono, (6) Genzyme, (7) Hoffmann-La Roche, (8) Immunic, (9) Janssen Pharmaceuticals, (10) Medday, (11) Merck, (12) Mylan, (13) Nervgen, (14) Novartis, (15) Sanofi-Genzyme, (16) Teva Pharmaceutical, (17) TG Therapeutics

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Travel to scientific meetings: (1) Actelion, (2) Alexion, (3) Biogen, (4) Bristol- Myers Squibb/Celgene, (5) EMD Serono, (6) Genzyme, (7) Hoffmann-La Roche, (8) Immunic, (9) Janssen Pharmaceuticals, (10) Medday, (11) Merck, (12) Mylan, (13) Nervgen, (14) Novartis, (15) Sanofi-Genzyme, (16) Teva Pharmaceutical, (17) TG Therapeutics, (18) Excemed, (19) MSIF and (20) NMSS.

    Editorial Boards:

    1. Member of

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Biogen, (2) Celgene, (3) Merck, (4) Novartis, (5) Roche, (6) Sanofi-Genzyme and (7) Teva Pharmaceutical.

    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. (1) Vice-president, Multiple Sclerosis Foundation of Barcelona (FEM) and (2) Vice-president, Fundació Cemcat

    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. Finn Sellebjerg, MD, PhD (sellebjerg{at}dadlnet.dk) and
    12. Scientific Advisory Boards:

    1. Participation in advisory boards for Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi Genzyme.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Travel grants or speaker honoraria from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, Teva.

    Editorial Boards:

    1. Section editor (immunology) for Multiple Sclerosis and Related Disorders since 2012

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Member of steering committee for clinical trials for Merck and Roche. Consulting work for Novartis.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Research support from Biogen, Merck, Novartis, Roche, Sanofi Genzyme.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Grant support from: Danish Multiple Sclerosis Society, the Johnsen Foundation, Foundation for Research in Neurology, the Friis 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

  12. Shohreh Issazadeh-Navikas, 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. The Lundbeck Foundation, Danish Multiple Sclerosis Society, Foundation for Research in Neurology. Belinda Carrion received a PhD fellowship from CONACYT- Mexico and the Lundbeck 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

  1. From the Biotech Research and Innovation Centre (BRIC) (B.C., Y.L., M.H., J.L., S.I.-N.), University of Copenhagen; Danish Multiple Sclerosis Center (J.R.C., C.A., P.S.S.), University of Copenhagen and Department of Neurology, Rigshospitalet; Blood Bank (M.H.D.), Copenhagen University Hospital, Denmark; Centre d'Esclerosi Múltiple de Catalunya (M.C.), Cemcat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d´Hebron (HUVH) – Universitat Autònoma de Barcelona, Barcelona, Spain; and Centre d'Esclerosi Múltiple de Catalunya (X.M.), Cemcat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d´Hebron (HUVH) – Universitat Autònoma de Barcelona, Spain; Danish Multiple Sclerosis Center, University of Copenhagen and Department of Neurology, Rigshospitalet, Denmark.
  1. Correspondence
    Dr. Issazadeh-Navikas shohreh.issazadeh{at}bric.ku.dk

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