Universität zu Köln

Kuerten, Stefanie ORCID: 0000-0001-6119-605X, Lanz, Tobias V., Lingampalli, Nithya, Lahey, Lauren J., Kleinschnitz, Christoph, Maeurer, Mathias, Schroeter, Michael, Braune, Stefan, Ziemssen, Tjalf ORCID: 0000-0001-8799-8202, Ho, Peggy P., Robinson, William H. and Steinmani, Lawrence (2020). Autoantibodies against central nervous system antigens in a subset of B cell-dominant multiple sclerosis patients. Proc. Natl. Acad. Sci. U. S. A., 117 (35). S. 21512 - 21519. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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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. AntiCNS 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 Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuerten, Stefanie UNSPECIFIED orcid.org/0000-0001-6119-605X UNSPECIFIED Lanz, Tobias V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lingampalli, Nithya UNSPECIFIED UNSPECIFIED UNSPECIFIED Lahey, Lauren J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleinschnitz, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Maeurer, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Braune, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziemssen, Tjalf UNSPECIFIED orcid.org/0000-0001-8799-8202 UNSPECIFIED Ho, Peggy P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, William H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinmani, Lawrence UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-321075
DOI:	10.1073/pnas.2011249117
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	117
Number:	35
Page Range:	S. 21512 - 21519
Date:	2020
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; BASIC-PROTEIN; NEUROMYELITIS-OPTICA; CEREBROSPINAL-FLUID; POTASSIUM CHANNEL; ANTIBODIES; MICROARRAYS; SERUM; AUTOANTIGEN; TARGET Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32107