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March 2021; 8 (2) ArticleOpen Access

Altered CSF Albumin Quotient Links Peripheral Inflammation and Brain Damage in MS

Marco Puthenparampil, Paula Tomas-Ojer, Thorsten Hornemann, Andreas Lutterotti, Ilijas Jelcic, Mario Ziegler, Andreas J. Hülsmeier, Carolina Cruciani, Wolfgang Faigle, Roland Martin, Mireia Sospedra
First published March 1, 2021, DOI: https://doi.org/10.1212/NXI.0000000000000951
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Article Information

vol. 8 no. 2 e951
DOI: 
https://doi.org/10.1212/NXI.0000000000000951
PubMed: 
33649179
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received June 3, 2020
  • Accepted in final form October 6, 2020
  • First Published March 1, 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. Marco Puthenparampil, MD, PhD (marco_puthen{at}hotmail.it),
    2. Paula Tomas-Ojer (paulatomasojer{at}gmail.com),
    3. Thorsten Hornemann, PhD (thorsten.hornemann{at}usz.ch),
    4. Andreas Lutterotti, MD (andreas.lutterotti{at}usz.ch),
    5. Ilijas Jelcic, MD, PhD (ilijas.jelcic{at}usz.ch),
    6. Mario Ziegler (mario.ziegler{at}usz.ch),
    7. Andreas J. Hülsmeier, PhD,
    8. Carolina Cruciani, PhD (carolina.cruciani{at}usz.ch),
    9. Wolfgang Faigle, PhD (wolfgang.faigle{at}usz.ch),
    10. Roland Martin, MD, PhD (roland.martin{at}usz.ch) and
    11. Mireia Sospedra, PhD
  1. Marco Puthenparampil, MD, PhD (marco_puthen{at}hotmail.it),
    2. Scientific Advisory Boards:

    1. Dr. Puthenparampil served on scientifici advisory board for Sanofi Genzyme, Biogen, Novartis.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Dr. Puthenparampil reports grants and personal fees from Novartis, grants and personal fees from Biogen IDEC, grants and personal fees from Almirall, grants from Teva, grants and personal fees from Genzyme Sanofi, grants from Merck Serono, outside the submitted work; .

    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. Paula Tomas-Ojer (paulatomasojer{at}gmail.com),
    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. 1. MSD Merck Sharp & Dohme, Clinical Research Associate, 1 year

    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. Thorsten Hornemann, PhD (thorsten.hornemann{at}usz.ch),
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. Patent "Methods for assaying disease characterised by dyslipidemia" (WO2011089146(A1); descibes the use of atypical sphingoid bases as diagnostic biomarkers Patent "Prevention and treatment of disease caused by elevated levels of deoxy-sphingolipids" ^(WO2011104298 (A1)); describes the therapeutic use of L-serine for the treatment of disease which are caused by or are associated with increased deoxy-sphingolipid levels

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. (1) Universityhospital Zürich( Dep. of Clinical Chemistry), Specialist in laboratory medicine (FAMH)

    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) The 7th Framework Program of the European Commission (“RESOLVE”, Project number 305707); PI; 2013 (2) The Swiss National Foundation SNF (Project 31003A_153390/1); PI; 2014

    Research Support, Academic Entities:

    1. Center for Integrated Human Physiology (ZIHP), University Zurich Research Framework Rare Diseases (RaDiz), University Zurich Rare Disease Initiative Zurich ("radiz", Clinical Research Priority Program for Rare Diseases), University of Zurich

    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. Andreas Lutterotti, MD (andreas.lutterotti{at}usz.ch),
    5. Scientific Advisory Boards:

    1. Almirall, Bayer, Biogen, Merck, Novartis, SanofiGenzyme, Celgene

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Travel support from European Charcot Foundation, Fundacio GAEM Biogen, Merck, Novartis, SanofiGenzyme, Celgene

    Editorial Boards:

    1. NONE

    Patents:

    1. Listed as an author on a University of Zurich patent on "Use of modified cells for the treatment of multiple sclerosis".

    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. Wyss Zurich, Swiss MS Society

    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. Ilijas Jelcic, MD, PhD (ilijas.jelcic{at}usz.ch),
    6. Scientific Advisory Boards:

    1. (1) Neuway (2) Merck (3) Novartis (4) Celgene (5) Sanofi- Aventis

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Novartis, speaker honoraria

    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. Mario Ziegler (mario.ziegler{at}usz.ch),
    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. Andreas J. Hülsmeier, PhD,
    8. Scientific Advisory Boards:

    1. Almirall, Bayer, Biogen, Merck, Novartis, SanofiGenzyme, Celgene

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Travel support from European Charcot Foundation, Fundacio GAEMBiogen, Merck, Novartis, SanofiGenzyme, Celgene

    Editorial Boards:

    1. NONE

    Patents:

    1. Listed as an author on a University of Zurich patent on "Use of modified cells for the treatment of multiple sclerosis".

    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. Wyss Zurich, Swiss MS Society

    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. Carolina Cruciani, PhD (carolina.cruciani{at}usz.ch),
    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. Wolfgang Faigle, PhD (wolfgang.faigle{at}usz.ch),
    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. University of Zurich, UZH

    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. Roland Martin, MD, PhD (roland.martin{at}usz.ch) and
    11. Scientific Advisory Boards:

    1. I have received personal compensation for advisory work to Biogen, Merck & Serono, Teva, Genzyme Sanofi-Aventis, CellProtect, Neuway, Roche, Third Rock Ventures

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. I have received personal compensation/honoraria for speaking at workshops or small meetings by Biogen and Merck & Serono, Novartis, Roche, Genzyme, Teva, Sanofi-Aventis.

    Editorial Boards:

    1. NONE

    Patents:

    1. Together with B. Bielekova, H. McFarland and T. Waldmann I am a coholder of a patent claiming the therapeutic efficacy of anti-CD25 monoclonal antibody treatment in combination with IFN-b in MS. This patent is owned by NIH, but the patent holders receive periodic royalties. I have received royalties in the last five years. I am also inventor or co-inventor on University Zurich-held patents in the context of antigen-specific tolerization with peptide-coupled cells and for vaccination methods against progressive multifocal leukoencephalopathy

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. I have been consulting for the Myelin Repair Foundation, The Weatherall Institute for Molecular Studies, University of Oxford, the German Research Society, and the Hertie Foundation. These are all non-profit academic or private institutions, foundations. I am a member of the Kuratorium of the Jung Foundation for Science, Hamburg, Germany, also a non-profit organization; the Swiss Multiple Sclerosis Society, also non-profit, and several other national MS societies, in each case non-profit.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Novartis has given us financial support (unrestricted grant) to examine the effects of fingolimod on immune responses against herpes viruses. Biogen has given us financial support (unrestricted grant) to study the effects of natalizumab on the intrathecal antibody response in MS. We have also received unrestricted support for the department of neuroimmunology and MS research from Roche.

    Research Support, Government Entities:

    1. Swiss National Science Foundation (throughout last 8 years). European Union Seventh Framework Program. European Research Council Advanced Grant. Clinical Research Priority Program Multiple Sclerosis of the University Zurich for the last 6 years.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. I hold stock of CellProtect, a small biotech Company; and of Cellerys, a company aiming at antigen-specific tolerization. If have not received any returns from the stock of these two entities

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. I had received royalty payments (periodically) from a NIH- Held patent on the use of anti-CD25 (daclizumab) in multiple sclerosis.

    Stock/Stock Options, Research Sponsor:

    1. I am Co-Founder and Co-Owner of Cellerys, a startup company out of Univ. Zurich, which is pursuing antigen-specific tolerization.

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Mireia Sospedra, PhD
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Invited editor of the special issue `Understanding and Elucidation of the Specificity of αβ-T cells`in Frontiers in Immunology

    Patents:

    1. Sospedra, M., Martin, R., Planas, R., Jelcic, I., Santos, R., Pinilla, C. IMMUNODOMINANT PROTEINS AND FRAGMENTS IN AUTOIMMUNE DISEASES. EP18180326.3 (2018). Jelcic, I., Martin, R., Schippling, S., Sospedra, M., Yousef, S. POLYOMA VIRUS JC PEPTIDES AND PROTEINS IN VACCINATION AND DIAGNOSTIC APPLICATIONS WO Patent 2,013,014,134 (2013)

    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

  1. From Neuroimmunology and MS Research (nims) (M.P., P.T.-O., A.L., I.J., M.Z., C.C., W.F., R.M., M.S.), Department of Neurology, University Hospital and University Zurich, Switzerland; Department of Neuroscience DNS (M.P.), University Hospital of Padova, Italy; and Institute for Clinical Chemistry (T.H., A.H.), University Hospital and University Zurich, Switzerland.
  1. Correspondence
    Dr. Sospedra Mireia.SospedraRamos{at}usz.ch
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