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Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood

Hohmann C, Milles B, Schinke M, Schroeter M, Ulzheimer J, Kraft P, Kleinschnitz C, Lehmann PV, Kuerten S (2014)

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Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 2

Article Number: 138

Journal Issue: 1

DOI: 10.1186/s40478-014-0138-2

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.

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APA:

Hohmann, C., Milles, B., Schinke, M., Schroeter, M., Ulzheimer, J., Kraft, P.,... Kuerten, S. (2014). Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood. Acta Neuropathologica Communications, 2(1). https://doi.org/10.1186/s40478-014-0138-2

MLA:

Hohmann, Christopher, et al. "Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood." Acta Neuropathologica Communications 2.1 (2014).

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