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Autoantibodies against central nervous system antigens in a subset of B cell-dominant multiple sclerosis patients

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination. The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previo...

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Main Authors: Kürten, Stefanie (Author) , Lanz, Tobias (Author) , Lingampalli, Nithya (Author) , Lahey, Lauren J. (Author) , Kleinschnitz, Christoph (Author) , Mäurer, Mathias (Author) , Schroeter, Michael (Author) , Braune, Stefan (Author) , Ziemssen, Tjalf (Author) , Ho, Peggy P. (Author) , Robinson, William H. (Author) , Steinman, Lawrence (Author)
Format: Article (Journal)
Language:English
Published: September 1, 2020
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2020, Volume: 117, Issue: 35, Pages: 21512-21518
ISSN:1091-6490
DOI:10.1073/pnas.2011249117
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.2011249117
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/doi/full/10.1073/pnas.2011249117
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Author Notes:Stefanie Kuerten, Tobias V. Lanz, Nithya Lingampalli, Lauren J. Lahey, Christoph Kleinschnitz, Mathias Mäurer, Michael Schroeter, Stefan Braune, Tjalf Ziemssen, Peggy P. Ho, William H. Robinson, and Lawrence Steinman
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Summary:Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination. The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previously introduced an enzyme-linked immunospot spot (ELISpot)-based assay to measure CNS antigen-specific B cells in the blood of MS patients and demonstrated its usefulness as a predictive biomarker for disease activity in measuring the successful outcome of disease-modifying therapies (DMTs). Here we used a planar protein array to investigate CNS-reactive antibodies in the serum of MS patients as well as in B cell culture supernatants after polyclonal stimulation. Anti-CNS antibody reactivity was evident in the sera of the MS cohort, and the antibodies bound a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, in individual patients. Immunoglobulin reactivity in supernatants of stimulated B cells was directed against a broad range of CNS antigens. A group of MS patients with a highly active B cell component was identified by the ELISpot assay. Those antibody reactivities remained stable over time. These assays with protein arrays identify MS patients with a highly active B cell population with antibodies directed against a swathe of CNS proteins.
Item Description:Gesehen am 15.12.2025
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.2011249117

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