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September 2021; 8 (5) ArticleOpen Access

Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome

Enric Monreal, Susana Sainz de la Maza, Lucienne Costa-Frossard, Paulette Walo-Delgado, Javier Zamora, José Ignacio Fernández-Velasco, Noelia Villarrubia, Mercedes Espiño, Daniel Lourido, Paloma Lapuente, Inmaculada Toboso, José Carlos Álvarez-Cermeño, Jaime Masjuan, Luisa María Villar
First published July 22, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001047
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Article Information

vol. 8 no. 5 e1047
DOI: 
https://doi.org/10.1212/NXI.0000000000001047
PubMed: 
34301819
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received February 25, 2021
  • Accepted in final form June 14, 2021
  • First Published July 22, 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. Enric Monreal, MD,
    2. Susana Sainz de la Maza, MD (susanasmc85{at}hotmail.com),
    3. Lucienne Costa-Frossard, MD (lufrossard{at}yahoo.es),
    4. Paulette Walo-Delgado, MD (pauletteesperanz.walo{at}salud.madrid.org),
    5. Javier Zamora, PhD (javierza{at}gmail.com),
    6. José Ignacio Fernández-Velasco, MSc (jfvelasco{at}salud.madrid.org),
    7. Noelia Villarrubia, PhD (noelia.villarrubia{at}salud.madrid.org),
    8. Mercedes Espiño, PhD (mercedes.espino{at}salud.madrid.org),
    9. Daniel Lourido, MD (louridodaniel{at}hotmail.com),
    10. Paloma Lapuente, MD (paloma.lapuente{at}salud.madrid.org),
    11. Inmaculada Toboso, PhD (inma.toboso.delamo{at}gmail.com),
    12. José Carlos Álvarez-Cermeño, PhD (josecarlos.alvarez{at}salud.madrid.org),
    13. Jaime Masjuan, PhD (jaime.masjuan{at}salud.madrid.org) and
    14. Luisa María Villar, PhD (luisamaria.villar{at}salud.madrid.org)
  1. Enric Monreal, MD,
    2. Scientific Advisory Boards:

    1. (1) Sanofi-Genzyme

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Biogen, funding for travel and speak to conference (2) Roche, funding for travel to conference (3) Almirall, funding for travel to conference (4) Sanofi-Genzyme, funding for travel to conference (5) Novartis, funding for travel to conference (6) Merck, funding for travel to conference

    Editorial Boards:

    1. NONE

    Patents:

    1. (1) Lymphocytes subsets ratio to predict autoimmunity in patients treated with Alemtuzumab.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. (1) Merck, promotional campaign

    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. Susana Sainz de la Maza, MD (susanasmc85{at}hotmail.com),
    3. Scientific Advisory Boards:

    1. (1) Almirall (Comercial entity) (2) Merck (Commercial entity) (3) Sanofi-Genzyme (Commercial entity)

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Biogen. Commercial entity. Speaker honoraria. (2) Merck. Commercial entity. Speaker honoraria. (3) Roche. Commercial entity. Speaker honoraria. (4) Sanofi-Genzyme. Commercial entity. Speaker honoraria. (5) Teva. Commercial entity. Speaker honoraria.

    Editorial Boards:

    1. NONE

    Patents:

    1. 17 382 331.1. Method for monitoring and predicting the efficacy of treatment in a multiple sclerosis patient España. 20/06/2017. FIBio-HRC.

    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. Lucienne Costa-Frossard, MD (lufrossard{at}yahoo.es),
    4. Scientific Advisory Boards:

    1. received payment for giving conferences, or travel expenses or research grants from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, Bayer and Novartis. The remaining authors declare no conflicts of interest.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. received payment for giving conferences, or travel expenses or research grants from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, Bayer and Novartis. The remaining authors declare no conflicts of interest.

    Editorial Boards:

    1. Editorial Board Member in American Journal of Psychiatry and Neuroscience

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. received payment for giving conferences, or travel expenses or research grants from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, Bayer and Novartis. The remaining authors declare no conflicts of interest.

    Speakers' Bureaus:

    1. received payment for giving conferences, or travel expenses or research grants from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, Bayer and Novartis. The remaining authors declare no conflicts of interest.

    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. Paulette Walo-Delgado, MD (pauletteesperanz.walo{at}salud.madrid.org),
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. Patent No. 20382988.2 - 1118 Predictive biomarkers of autoimmunity in patients treated with alemtuzumab

    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. Javier Zamora, PhD (javierza{at}gmail.com),
    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. José Ignacio Fernández-Velasco, MSc (jfvelasco{at}salud.madrid.org),
    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. Noelia Villarrubia, PhD (noelia.villarrubia{at}salud.madrid.org),
    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. (1)Fondo para la Investigación Sanitaria from the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación (Spain) and Fondo Europeo de Desarrollo Regional (FEDER), grant number: RD16/0015/0001, 2019-2021 (2)Fondo para la Investigación Sanitaria from the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación (Spain) and Fondo Europeo de Desarrollo Regional (FEDER), grant number: PI18/00572, 2017-2021

    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. Mercedes Espiño, PhD (mercedes.espino{at}salud.madrid.org),
    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. Daniel Lourido, MD (louridodaniel{at}hotmail.com),
    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. Paloma Lapuente, MD (paloma.lapuente{at}salud.madrid.org),
    11. 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

  11. Inmaculada Toboso, PhD (inma.toboso.delamo{at}gmail.com),
    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. José Carlos Álvarez-Cermeño, PhD (josecarlos.alvarez{at}salud.madrid.org),
    13. Scientific Advisory Boards:

    1. Genzyme, Araclon Biotech

    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

  13. Jaime Masjuan, PhD (jaime.masjuan{at}salud.madrid.org) and
    14. 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

  14. Luisa María Villar, PhD (luisamaria.villar{at}salud.madrid.org)
    15. Scientific Advisory Boards:

    1. Genzyme, Biogen, Merck, Novartis

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Biogen: Funding for travel or speaker honorariaMerck: Funding for travel or speaker honorariaNovartis: Funding for travel or speaker honorariaGenzyme: Funding for travel or speaker honorariaRoche: Funding for travel or speaker honoraria

    Editorial Boards:

    1. NONE

    Patents:

    1. Biomarker for selecting good responders to IFN beta in multiple sclerosis

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. I have received payment for consultancies fromBiogen Idec, Merck, Novartis, (Commercial entities)

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Genzyme; Merck; Biogen; Roche

    Research Support, Government Entities:

    1. Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (ISCIII). Grant N. PI18/00572 for the research in MS. Years 2019-2021

    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 (E.M., S.S.d.l.M., L.C.-F., J.C.Á.-C., J.M.), and Department of Immunology (P.W.-D., J.I.F.-V., N.V., M.E., P.L., I.T., L.M.V.), Hospital Universitario Ramón y Cajal, REEM, IRYCIS; Clinical Biostatistics Unit (J.Z.), Hospital Universitario Ramón y Cajal, IRYCIS, CIBERESP, Madrid, Spain; Institute of Metabolism and System Research (J.Z.), University of Birmingham, United Kingdom; and Department of Radiology (D.L.), Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
  1. Correspondence
    Dr. Monreal enricmonreal{at}outlook.com
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