Universität zu Köln

Hohmann, Christopher, Milles, Bianca, Schinke, Michael, Schroeter, Michael, Ulzheimer, Jochen, Kraft, Peter, Kleinschnitz, Christoph ORCID: 0000-0002-1650-8875, Lehmann, Paul V. and Kuerten, Stefanie (2014). Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood. Acta Neuropathol. Commun., 2. LONDON: BIOMED CENTRAL LTD. ISSN 2051-5960

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Abstract

Introduction: B cells are attracting increasing attention in the pathogenesis of multiple sclerosis (MS). B cell-targeted therapies with monoclonal antibodies or plasmapheresis have been shown to be successful in a subset of patients. Here, patients with either relapsing-remitting (n = 24) or secondary progressive (n = 6) MS presenting with an acute clinical relapse were screened for their B cell reactivity to brain antigens and were re-tested three to nine months later. Enzyme-linked immunospot technique (ELISPOT) was used to identify brain-reactive B cells in peripheral blood mononuclear cells (PBMC) directly ex vivo and after 96 h of polyclonal stimulation. Clinical severity of symptoms was determined using the Expanded Disability Status Scale (EDSS). Results: Nine patients displayed B cells in the blood producing brain-specific antibodies directly ex vivo. Six patients were classified as B cell positive donors only after polyclonal B cell stimulation. In 15 patients a B cell response to brain antigens was absent. Based on the autoreactive B cell response we categorized MS relapses into three different patterns. Patients who displayed brain-reactive B cell responses both directly ex vivo and after polyclonal stimulation (pattern I) were significantly younger than patients in whom only memory B cell responses were detectable or entirely absent (patterns II and III; p = 0.003). In one patient a conversion to a positive B cell response as measured directly ex vivo and subsequently also after polyclonal stimulation was associated with the development of a clinical relapse. The evaluation of the predictive value of a brain antigen-specific B cell response showed that seven of eight patients (87.5%) with a pattern I response encountered a clinical relapse during the observation period of 10 months, compared to two of five patients (40%) with a pattern II and three of 14 patients (21.4%) with a pattern III response (p = 0.0005; hazard ratio 6.08 (95% confidence interval 1.87-19.77). Conclusions: Our data indicate actively ongoing B cell-mediated immunity against brain antigens in a subset of MS patients that may be causative of clinical relapses and provide new diagnostic and therapeutic options for a subset of patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hohmann, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Milles, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Schinke, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Ulzheimer, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraft, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleinschnitz, Christoph UNSPECIFIED orcid.org/0000-0002-1650-8875 UNSPECIFIED Lehmann, Paul V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuerten, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-451625
DOI:	10.1186/s40478-014-0138-2
Journal or Publication Title:	Acta Neuropathol. Commun.
Volume:	2
Date:	2014
Publisher:	BIOMED CENTRAL LTD
Place of Publication:	LONDON
ISSN:	2051-5960
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45162