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March 2021; 8 (2) ArticleOpen Access

Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS

Thanos Tsaktanis, Tobias Beyer, Lucy Nirschl, Mathias Linnerbauer, Verena Grummel, Mathias Bussas, Emily Tjon, Mark Mühlau, Thomas Korn, Bernhard Hemmer, Francisco J. Quintana, Veit Rothhammer
First published December 24, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000933
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Article Information

vol. 8 no. 2 e933
DOI: 
https://doi.org/10.1212/NXI.0000000000000933
PubMed: 
33361385
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received June 12, 2020
  • Accepted in final form October 29, 2020
  • First Published December 24, 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-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. Thanos Tsaktanis, MD (ge56naq{at}mytum.de),
    2. Tobias Beyer, MSc (t.beyer{at}tum.de),
    3. Lucy Nirschl, BS (lucy.nirschl{at}tum.de),
    4. Mathias Linnerbauer, MSc (mathias.linnerbauer{at}gmail.com),
    5. Verena Grummel (v.grummel{at}tum.de),
    6. Mathias Bussas, MSc (matthias.bussas{at}mri.tum.de),
    7. Emily Tjon, MSc (emilyctjon{at}gmail.com),
    8. Mark Mühlau, MD (mark.muehlau{at}tum.de),
    9. Thomas Korn, MD (thomas.korn{at}tum.de),
    10. Bernhard Hemmer, MD (hemmer{at}tum.de),
    11. Francisco J. Quintana, PhD (fquintana{at}rics.bwh.harvard.edu) and
    12. Veit Rothhammer, MD
  1. Thanos Tsaktanis, MD (ge56naq{at}mytum.de),
    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. Tobias Beyer, MSc (t.beyer{at}tum.de),
    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. German Research Foundation (DFG, RO4866/2-1)

    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. Lucy Nirschl, BS (lucy.nirschl{at}tum.de),
    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. Mathias Linnerbauer, MSc (mathias.linnerbauer{at}gmail.com),
    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. Verena Grummel (v.grummel{at}tum.de),
    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. Mathias Bussas, MSc (matthias.bussas{at}mri.tum.de),
    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. Emily Tjon, MSc (emilyctjon{at}gmail.com),
    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. Mark Mühlau, MD (mark.muehlau{at}tum.de),
    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. German Competence Network Multiple Sclerosis (German Ministry for Research and Education, 01GI1604A), PI, 3 yearsGerman Research Foundation (DFG SPP2177, Radiomics: Next Generation of Biomedical Imaging, project number 428223038, 3 years

    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. Thomas Korn, MD (thomas.korn{at}tum.de),
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Novartis (2) Alexion

    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. Deutsche Forschungsgemeinschaft (DFG): KO2964/2-1, KO2964/3-1, KO2964/4-1, KO2964/5-1, SFB1054- B06, TR128-A07, TR274-A01, Synergy EXC2145. European Research Council (ERC): CoG647215

    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. Bernhard Hemmer, MD (hemmer{at}tum.de),
    11. Scientific Advisory Boards:

    1. Advisory Boards for Novartis, he has served as DMSC member for AllergyCare, TG Therapeutics and Polpharma Biologics

    Gifts:

    1. Me or my institution have received speaker honoraria from Desitin

    Funding for travel or speaker honoraria:

    1. Excemed

    Editorial Boards:

    1. Editorial board member of Jama Neurology, Experimental Neurology and Multiple sclerosis Journal

    Patents:

    1. I hold part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulati on of MS patients and one for genetic determinants of neutralizing antibodies to interferon β

    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) Regeneron - not related

    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

  11. Francisco J. Quintana, PhD (fquintana{at}rics.bwh.harvard.edu) and
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. 2012 Editorial Board Member Systems Biomedicine 2012 Editorial Board Member Inmunologia (Spain) 2013- Associate Editor Immunology (UK) 2013- Senior Editorial Board Member American Journal of Clinical and Experimental Immunology 2014- Advisory Board MemberSeminars in Immunopathology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Teva, Blueprint Medicines, AnTolRx

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. 1. EMD-Serono 2. Sanofi 3. Novartis 4. Teva 5. ONO

    Research Support, Government Entities:

    1. (1) NIH, R00 AI075285-01A2, Role PI, 2010-2012, (2) NIH, R01 AI093903-01, Role PI, 2011–2016, (3) NIH, K99AI075285-01A2, Role PI, 2009-2010, (4) NIH, 1R01NS102807-01A1, role PI, 09/01/18 – 08/31/23, (5) NIH, R01 ES025530-02, role PI, 06/01/16 – 05/31/21, (6) NMSS, JF 2161-A-5, role PI, 07/01/14 – 06/30/19, (7) American Cancer Soc., 126566-RSG-14-198-01-LIB, role PI, 01/01/15 – 12/31/18, (8) NMSS, RR-1601-07385, role PI, 10/01/16 – 09/30/19, (9) Israel Cancer Research Fund, 15-975-ICG, role PI, 09/01/16 – 08/30/19, (10) NIH-NIAID, 1R01AI126880-01A1, role PI, 02/01/17 – 01/31/22, (11) NIH-NIAID, 2R01HL095722-06A1, role PI, 09/01/15 – 08/31/20, (12) NMSS, PA-1604-08459, role PI, 06/01/17 – 05/31/21, (13) NMSS, PA-1604-08459, role PI, 06/01/17 – 05/31/21, (14) King Abdulaziz City for Science & Technology, 117427, role PI, 06/01/17 – 05/31/18, (15) NIH, 5R01DK108894-01, role Co-I, 02/01/17 – 01/31/22,

    Research Support, Academic Entities:

    1. (1) Harvard Medical School, Diversity and Community Partnership Faculty Fellowship, Role PI, 2010-2012, (2) BADERC, Pilot and Feasibility Award (Quintana), Role PI, 2010-2012

    Research Support, Foundations and Societies:

    1. (1) NMSS, RG4111A1/1, Role PI, 2009-2012, (2) NMSS, RG4048A11, Role Research Associate, 2008-2011

    Stock/Stock Options/Board of Directors Compensation:

    1. AnTolRx

    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. Veit Rothhammer, MD
    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. Novartis Pharmaceuticals, Research Support

    Research Support, Government Entities:

    1. German Research Foundation, RO4866, PI, 2018 - 2023 European Research Council, HICI, 2020 - 2024

    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 Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.
  1. Correspondence
    Dr. Rothhammer veit.rothhammer{at}fau.de
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