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

Kürten S, Lanz TV, Lingampalli N, Lahey LJ, Kleinschnitz C, Mäurer M, Schroeter M, Braune S, Ziemssen T, Ho PP, Robinson WH, Steinman L (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 117

Pages Range: 21512-21518

Journal Issue: 35

DOI: 10.1073/pnas.2011249117

Abstract

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.

Authors with CRIS profile

Stefanie Kürten Lehrstuhl für Mikroskopische Anatomie und Molekulare Zellbiologie

Involved external institutions

Stanford University US United States (USA) (US) VA Palo Alto Health Care System US United States (USA) (US) Universitätsklinikum Essen DE Germany (DE) Fraunhofer-Institut für Biomedizinische Technik (IBMT) / Fraunhofer Institute for Biomedical Engineering DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE)

How to cite

APA:

Kürten, S., Lanz, T.V., Lingampalli, N., Lahey, L.J., Kleinschnitz, C., Mäurer, M.,... Steinman, L. (2020). Autoantibodies against central nervous system antigens in a subset of B cell-dominant multiple sclerosis patients. Proceedings of the National Academy of Sciences of the United States of America, 117(35), 21512-21518. https://doi.org/10.1073/pnas.2011249117

MLA:

Kürten, Stefanie, et al. "Autoantibodies against central nervous system antigens in a subset of B cell-dominant multiple sclerosis patients." Proceedings of the National Academy of Sciences of the United States of America 117.35 (2020): 21512-21518.

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