14694
2016
eng
105
4
8
article
1
2017-04-07
--
--
The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis
There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.
Viruses
10.3390/v8040105
urn:nbn:de:bvb:20-opus-146946
Viruses 2016, 8, 105; doi:10.3390/v8040105
Marie Wunsch
Christopher Hohmann
Bianca Milles
Christina Rostermund
Paul V. Lehmann
Michael Schroeter
Antonios Bayas
Jochen Ulzheimer
Mathias Mäurer
Süleyman Ergün
Stefanie Kuerten
eng
uncontrolled
B cells
eng
uncontrolled
CMV
eng
uncontrolled
EBV
eng
uncontrolled
ELISPOT
eng
uncontrolled
MS
Krankheiten
open_access
Institut für Anatomie und Zellbiologie
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14694/088_Wunsch_viruses-08-00105.pdf
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