12612
2014
eng
138
2
article
1
2016-01-28
--
--
Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood
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.
Acta Neuropathologica Communications
10.1186/s40478-014-0138-2
urn:nbn:de:bvb:20-opus-126124
Acta Neuropathologica Communications 2014, 2:138. doi:10.1186/s40478-014-0138-2
Christopher Hohnmann
Bianca Milles
Michael Schinke
Michael Schroeter
Jochen Ulzheimer
Peter Kraft
Christoph Kleinschnitz
Paul V. Lehmann
Stefanie Kuerten
eng
uncontrolled
predictive value
eng
uncontrolled
MS
eng
uncontrolled
ELISPOT
eng
uncontrolled
B cells
eng
uncontrolled
relapse
Medizin und Gesundheit
open_access
Institut für Anatomie und Zellbiologie
Neurologische Klinik und Poliklinik
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12612/Kuerten_s40478-014-0138-2.pdf
12058
2014
eng
138
2
article
1
2015-10-21
--
--
Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood
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.
Acta Neuropathologica Communications
10.1186/s40478-014-0138-2
2051-5960
25597707
urn:nbn:de:bvb:20-opus-120580
Acta Neuropathologica Communications 2014, 2:138. doi:10.1186/s40478-014-0138-2
Christopher Hohmann
Bianca Milles
Michael Schinke
Michael Schroeter
Jochen Ulzheimer
Peter Kraft
Christoph Kleinschnitz
Paul V. Lehmann
Stefanie Kuerten
eng
uncontrolled
ELISPOT
eng
uncontrolled
MS
eng
uncontrolled
predictive value
eng
uncontrolled
relapse
eng
uncontrolled
B cells
Medizin und Gesundheit
open_access
Institut für Anatomie und Zellbiologie
Neurologische Klinik und Poliklinik
Institut für Klinische Epidemiologie und Biometrie
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12058/104_Hohmann_Acta_Neuropatholica_Communications.pdf