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medRxiv

Comprehensive cerebrospinal fluid analysis indicates key roles for B cells in multiple sclerosis

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  • January 6, 2025
  • Chotima Boettcher, et al.  Charite, Berlin
Topic/Product:
CNS Disease Panel 120, Inflammation Panel 250, Neurology
Disease Area:
Multiple Sclerosis (MS)
Sample Type:
CSF

Abstract

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative disease of the central nervous system (CNS) with a multifaceted pathophysiology, likely involving a variety of mechanisms and effectors. To characterize the spectrum of cellular and molecular factors
involved in MS at an unprecedented level, we here performed a comprehensive analysis of cerebrospinal fluid (CSF) and peripheral blood using multiple high-dimensional technologies,
including mass cytometry, metabolomics and proteomics (NULISA and Olink Explore® 3072).
Enriched B cells and proteins involved in B cell functions in the CSF separated MS patients
from other neurological disease entities. Specific B cell subpopulations and molecular markers
including gut-microbiota-derived metabolites and neurofilament light protein, a marker of
neuroaxonal damage, in CSF correlated with clinical (acute vs. stable disease) and/or
radiological (gadolinium enhancement) disease activity. Altogether, unbiased broad
phenotyping suggests key roles of diverse B subpopulations and B cell related molecular
markers in MS, which are associated with both, inflammatory and degenerative aspects of the
disease and may serve as disease activity and treatment response biomarkers.

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Authors & Affiliations

Camila Fernández-Zapata1,2,18, Carolin Otto3,18, Gerardina Gallaccio1,2,18, Qianlan Chen1,2,4,18,
Meng Wang1,2, Burulça Uluvar5, Matteo Teves6, Claudia Samol6, Maria Buthut7, Fabian R. Bösl3,
Adeline Dehlinger1,2, GueHo Jang1,2, Christian Böttcher1,2, Helena Radbruch8, Josef
Priller9,10,11,12, Patrick Schindler3, Catarina Raposo13, Sven Shippling13, Rosetta Pedotti13,
Desiree Kunkel14, Maik Pietzner5,15,16, Christiana Franke3, Peter J. Oefner6, Wolfram Gronwald6,
Harald Prüß3,10, Johannes Lohmeier17,19, Friedemann Paul1,2,3,4,19, Klemens Ruprecht3,19,
Chotima Böttcher1,2,19

  1. Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center
    for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin,
    Germany.
  2. Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
  3. Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  4. Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  5. Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
  6. Institute of Functional Genomics, University of Regensburg, Am Biopark 9, 93053 Regensburg, Germany.
  7. Department of Psychiatry and Neurosciences, Clinical Neurotechnology Lab, Neuroscience
    Research Center, Charité – Universitätsmedizin Berlin, Berlin, Germany.
  8. Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.
  9. Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  10. German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
  11. Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich and German Center for Mental Health (DZPG), Munich, Germany.
  12. University of Edinburgh and UK DRI, Edinburgh, UK.  
  13. F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  14. Flow & MassCytometry Core Facility, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin 13353, Germany.
  15. Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
  16. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
  17. Institute of Neuroradiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  18. These authors contributed equally to this work.
  19. These authors jointly directed this work.
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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.