Identification of a B cell-dependent subpopulation of multiple sclerosis by measurements of brain-reactive B cells in the blood

Küerten, Stefanie; Pommerschein, G; Barth, Stefanie K.; Hohmann, Christopher; Milles, Bianca; Sammer, F.; Duffy, Cathrina E.; Wunsch, Marie; Rovituso, Damiano M.; Schroeter, Michael; Addicks, Klaus; Kaiser, Claudia; Lehmann, Paul

doi:10.1016/j.clim.2014.02.014

Cited by 28 publications

(33 citation statements)

References 19 publications

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“…In our previous work we have demonstrated that the detection of brain antigen-specific B cells in the PBMC population permitted the identification of a B cell-dependent subtype of MS [15]. These data were in line with earlier reports that showed the presence of proteolipid protein (PLP)- and MOG-specific B cells in the blood and cerebrospinal fluid (CSF) of patient with MS using the ELISPOT approach [29,30].…”

Section: Discussionsupporting

confidence: 85%

“…Twelve of the healthy donors were retested on the consecutive day with similar results to account for day-to-day variation. The cut-off value for a brain antigen-specific B cell response after polyclonal stimulation was set to > 4.5 spots as previously established [15]. Serum samples were considered positive when the OD was at least five standard deviations above the mean value of a cohort of 69 healthy control donors.…”

Section: Methodsmentioning

confidence: 99%

“…These B cells only occurred in MS patients and were absent in healthy donors and in patients with other inflammatory and non-inflammatory neurological diseases as well as other autoimmune disorders [15]. Our previous analyses focused on measurements of the brain antigen-specific B cell response after 96 h of polyclonal stimulation.…”

Section: Introductionmentioning

confidence: 99%

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

Hohmann

Milles

Schinke

et al. 2014

acta neuropathol commun

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IntroductionB 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).ResultsNine 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).ConclusionsOur 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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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

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

Hohmann

Milles

Schinke

et al. 2014

acta neuropathol commun

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“…Although the involvement of B-lymphocytes in the pathogenesis of MS has been a focus in recent years, a full characterization of B-cell subpopulations in peripheral blood of MS patients is still lacking (34,35). Most of the studies on B-cells are focused on their changes in response to treatments (36,37).…”

Section: B-cell Subpopulationsmentioning

confidence: 99%

Immunomonitoring Lymphocyte Subpopulations in Multiple Sclerosis Patients

Teniente‐Serra¹,

Ramo‐Tello

Martı́nez-Cáceres

2017

Multiple Sclerosis: Perspectives in Treatment and Pathogenesis

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Abstract:Advances in the understanding of pathogenic mechanisms of diseases have led to the defining of new biomarkers for diagnosis, prognosis, and therapy response. In this context, flow cytometry has been positioned as one of the most useful technologies for monitoring immune-mediated diseases, such as multiple sclerosis (MS), allowing a detailed analysis of lymphocyte subpopulations in peripheral blood. The autoimmune inflammatory response in MS results in changes in lymphocyte subpopulations that might be useful as surrogate markers for the evaluation of disease activity, progression, and monitoring of therapy response. This chapter discusses the role of T-lymphocyte and B-lymphocyte subpopulations in MS pathogenesis, the effect of MS treatments on these subsets, and their potential usefulness as biomarkers of treatment response.

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“…Activated B cells, memory B cells, regulatory B cells, and plasma cells have been found in peripheral blood and/or cerebrospinal fluid (CSF) of patients with RRMS and patients with clinically isolated syndrome (CIS) (5,6,7,8,9). However, very little is known on the alteration of B cell subsets in the transitional stage of MS, when patients progress from RRMS to secondary progressive MS (SPMS).…”

Section: Introductionmentioning

confidence: 99%

Flow Cytometry Analysis of Peripheral Blood B Cell Distribution of Patients with Multiple Sclerosis

Yılmaz¹,

Tura²,

Ulusoy³

et al. 2017

tnd

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Objective: Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by autoimmune inflammation and neurodegeneration. Damage to the CNS is thought to be mediated predominantly by activated pro-inflammatory T cells and antibody secreting B cells. Strong evidence of B cell functions in MS pathogenesis has come from trials of B cell-depleting treatment. In this study, the peripheral blood frequencies of B cell subsets were measured using flow cytometry in patients to determine the disease-specific B cell differences that might be associated with the evolution to progressive forms of MS. Materials and Methods:Peripheral blood mononuclear cells were separated from patients and healthy controls [relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS)]. Cells were stained with anti-human monoclonal antibodies (CD19-APC, CD27-FITC, IgD-APC/Cy7, CD138-PE, CD24-PerCP and CD38-Alexa fluor 700), and analyzed using flow cytometry.Results: There were no significant differences between the MS group and healthy controls by means of peripheral blood frequencies of B cells, immature, naïve, classic memory, plasma, plasmablasts, and regulatory B cells. Only higher naïve B cell frequency tendency was determined in patients with RRMS as compared with patients with SPMS and healthy controls. Conclusion:Peripheral blood B cell subset measurements are not likely to be used as a biomarker for prediction of disease progression. Although B cells have a well-known pathogenic significance, B cell population alterations do not occur during the progression of the disease. Keywords: Multiple sclerosis, B cell, peripheral bloodAmaç: Multipl skleroz (MS), bir merkezi sinir sistemi hastalığıdır ve otoimmün inflamasyon ve nörodejenerasyon ile karakterizedir. Hastalıkta aktif olan enflamasyon ve proinflamatuar T hücresi dışında antikor yapan B hücrelerinin de rolü büyüktür. Periferik B hücrelerinin MS hastalığındaki rolü, B hücrelerinin deplesyonu ile elde edilen bulgulara dayanmaktadır. Çalışmamızda periferik kandaki B hücre alt tiplerinin akım sitometrisi ile belirlenmesi ve hastalık alt gruplarındaki olası farklarının belirlenmesi hedeflendi. Gereç ve Yöntem: MS hasta grubu [relapsing-remitting MS (RRMS) ve sekonder progresif MS (SPMS)] ve sağlıklı donörlerden periferik kan mononükleer hücreleri izole edildi. Bu hücreler, B hücresine spesifik monoklonal antikorlar ile (CD19-APC, CD27-FITC, IgD-APC/Cy7, CD138-PE, CD24-PerCP ve CD38-Alexa fluor 700) işaretlendi ve akım sitometrisi ile değerlendirildi. Abstract Öz 219Original Article / Özgün Araştırma DO I:10.4274/tnd.87523 Turk J Neurol 2017;23:219-224

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Identification of a B cell-dependent subpopulation of multiple sclerosis by measurements of brain-reactive B cells in the blood

Cited by 28 publications

References 19 publications

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

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

Immunomonitoring Lymphocyte Subpopulations in Multiple Sclerosis Patients

Flow Cytometry Analysis of Peripheral Blood B Cell Distribution of Patients with Multiple Sclerosis

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