scholarly journals The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Damiano M. Rovituso ◽  
Cathrina E. Duffy ◽  
Michael Schroeter ◽  
Claudia C. Kaiser ◽  
Christoph Kleinschnitz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Glatiramer Acetate ◽  
Cell Response ◽  
Brain Antigen ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

Thymosin-α1 expands deficient IL-10-producing regulatory B cell subsets in relapsing–remitting multiple sclerosis patients

2017 ◽  
Vol 24 (2) ◽  
pp. 127-139 ◽  
Author(s):  
Elena Giacomini ◽  
Fabiana Rizzo ◽  
Marilena P Etna ◽  
Melania Cruciani ◽  
Rosella Mechelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Cell Response ◽  
Thymosin Α1 ◽  
Regulatory B Cell ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
B Cell Subsets ◽  
Relapsing Remitting Multiple Sclerosis

Background: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain B cell abnormalities by directly targeting this lymphocyte population. Objectives: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of B cell response in relapsing–remitting multiple sclerosis (RRMS) and having found a low serum level of Thymosin-α1 (Tα1) in patients, we investigated whether the addition of this molecule to peripheral blood mononuclear cells (PBMCs) would influence the expansion of regulatory B cell subsets, known to dampen autoimmune inflammation. Methods: Serum Tα1 level was measured by enzyme immunoassay. Cytokine expression was evaluated by Cytometric Bead Array (CBA), enzyme-linked immunosorbent assay (ELISA), and real-time reverse transcription polymerase chain reaction (RT-PCR). B cell subsets were analyzed by flow cytometry. Results: Tα1 pre-treatment induces an anti-inflammatory status in TLR7-stimulated RRMS PBMC cultures, reducing the secretion of pro-inflammatory interleukin (IL)-6, IL-8, and IL-1β while significantly increasing the regulatory IL-10 and IL-35. Indeed, Tα1 treatment enhanced expansion of CD19+CD24+CD38hi transitional-immature and CD24low/negCD38hi plasmablast-like regulatory B cell subsets, which likely inhibit both interferon (IFN)-γ and IL-17 production. Conclusion:: Our study reveals a deficient ability of B cells from MS patients to differentiate into regulatory subsets and unveils a novel anti-inflammatory and repurposing potential for Tα1 in MS targeting B cell response.

scholarly journals B-Cell Activity Predicts Response to Glatiramer Acetate and Interferon in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. e980
Author(s):  
Sabine Tacke ◽  
Stefan Braune ◽  
Damiano M. Rovituso ◽  
Tjalf Ziemssen ◽  
Paul V. Lehmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Clinical Response ◽  
Glatiramer Acetate ◽  
Peripheral Blood ◽  
Predictive Value ◽  
Cell Activity ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

ObjectiveWe investigated the predictive value of the enzyme-linked immunospot technique (ELISPOT) in identifying patients with relapsing-remitting multiple sclerosis (RRMS) who will respond to treatment with glatiramer acetate (GA) or interferon-β (IFN-β), based on the brain-reactive B-cell activity of peripheral blood cells.MethodsIn this retrospective, cross-sectional, real-world multicenter study, we identified patients with RRMS in the NeuroTransData MS registry and stratified them based on their documented treatment response (relapse-free in the first 12 months of treatment) to GA or IFN-β. The GA group comprised 73 patients who responded to GA and 35 nonresponders. The IFN-β group comprised 62 responders to IFN-β and 37 nonresponders. Patients with previous or current therapy affecting B-cell activity were excluded. We polyclonally stimulated mononuclear cells from peripheral blood samples (collected after participant selection) and investigated brain-reactive B-cell activity after incubation on brain tissue lysate-coated ELISPOT plates. Validity metrics of the ELISPOT testing results were calculated (Python 3.6.8) in relation to the clinical responsiveness in the 2 treatment groups.ResultsThe ELISPOT B-cell activity assay showed a sensitivity of 0.74, a specificity of 0.76, a positive predictive value of 0.78, a negative predictive value of 0.28, and a diagnostic OR of 8.99 in predicting clinical response to GA vs IFN-β therapy in patients with RRMS.ConclusionMeasurement of brain-reactive B-cell activity by ELISPOT provides clinically meaningful predictive probabilities of individual patients' treatment response to GA or IFN-β. The assay has the potential to improve the selection of optimal first-line treatment for individual patients with RRMS.Classification of EvidenceThis study provides Class II evidence that in patients with RRMS, the brain reactivity of their peripheral-blood B cells predicts clinical response to GA and IFN-β.

scholarly journals Lymphocyte subtypes in relapsing–remitting multiple sclerosis patients treated with dimethyl fumarate

2017 ◽  
Vol 3 (2) ◽  
pp. 205521731770293 ◽  
Author(s):  
C Chaves ◽  
R Ganguly ◽  
C Ceresia ◽  
A Camac
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
B Cell ◽  
Dimethyl Fumarate ◽  
Normal Lymphocyte ◽  
Cell Counts ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Recent data suggest that lymphopenia is more prevalent than reported in relapsing–remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF). Objective The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia. Method A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1, n = 35) and normal lymphocyte counts (G2, n = 24). Results Fifty-nine patients were identified, with mean age 49, 71.2% females, and average DMF duration 20 months. Age, sex, baseline white blood count, disease and treatment durations were similar between groups. Prior interferon therapy and baseline lower normal lymphocyte counts were more frequent in G1. Mean lymphocyte counts were 0.8 ± 0.2 × 109/L in G1 and 1.6 ± 0.3 × 109/L in G2. CD3+, CD4+, and CD8+ T cell mean counts were lower ( p < 0.0001), while CD4/CD8 ratio higher ( p = 0.03) in G1 than G2. Mean CD19 + B cell counts were normal; however, values were lower in G1 ( p = 0.04). After adjusting for confounders, significantly positive correlations were noted between lymphocyte counts and CD3 + , CD4+, CD8+ T, and B cell counts. Negative correlation was observed between lymphocyte counts and CD4/CD8 ratio driven by low CD8+ T cell counts. Conclusion DMF treatment predominantly impacts T cells, in particular CD8+ subtype. This finding may have implications in this population’s immunocompetence.

scholarly journals Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing–remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study

2016 ◽  
Vol 23 (6) ◽  
pp. 818-829 ◽  
Author(s):  
Omar Khan ◽  
Peter Rieckmann ◽  
Alexey Boyko ◽  
Krzysztof Selmaj ◽  
Natalia Ashtamker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Gray Matter Volume ◽  
Low Frequency ◽  
Open Label ◽  
Treatment Benefit ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: The 1-year placebo-controlled (PC) phase of the Glatiramer Acetate Low-Frequency Administration (GALA) study showed that glatiramer acetate 40 mg/mL three times weekly (GA40) significantly reduced annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity in patients with relapsing–remitting multiple sclerosis. Patients completing the PC phase were invited to an open-label (OL) extension. Objective: To evaluate the effects of early start (ES) and delayed start (DS) of GA40 over 3 years. Methods: A total of 97.2% of patients completing the PC phase received GA40 in the OL extension. ES ( n = 943) patients received GA40 throughout; DS ( n = 461) patients received placebo during the PC phase and GA40 during the OL phase. Relapse, MRI, disease progression, and safety were evaluated. Results: A total of 1041 patients completed 3 years of follow-up. During the OL phase, ES and DS patients showed comparable ARRs (0.20–0.22) and similar numbers of gadolinium-enhancing T1 ( p = 0.49) and new or enlarging T2 lesions ( p = 0.51) at Year 3. ES patients showed significantly smaller changes in gray matter volume than DS patients from Months 12 to 36 (mean difference, 0.371%; p = 0.015), with similar trend in whole-brain volume ( p = 0.080). Adverse events were mild, consistent with the well-established glatiramer acetate (GA) safety profile. Conclusion: GA40 conferred treatment benefit over 3 years: sustained low ARR and lesion activity and favorable safety.

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