Wednesday, 28 January 2015

B cells and their role in relapse

Hohmann C, Milles B, Schinke M, Schroeter M, Ulzheimer J, Kraft P, Kleinschnitz C, Lehmann PV, Kuerten S. Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood.
Acta Neuropathol Commun. 2014 ;2(1):138.


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) taken directly from the blood  and after 96 h of 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. Six patients were classified as B cell positive donors only after 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 from the blood 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.

This data indicate actively ongoing B cell-mediated immunity against brain antigens in a small subset of people with MS and they appear around the time of relapse whether this causative, is up for debate but will particularly interesting in those sceientists looking at B cell autoimmunity




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