scholarly journals Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Evgeniy Evdoshenko ◽  
Alexey Maslyanskiy ◽  
Sergey Lapin ◽  
Leonid Zaslavsky ◽  
Ruth Dobson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Combined Therapy ◽  
Cell Subset ◽  
Cell Subpopulation ◽  
Cell Populations ◽  
B Cell Depletion ◽  
Memory B Cell ◽  
Therapeutic Protocol ◽  
Observation Period

Background. Mitoxantrone (MTX) and Rituximab (RTX) are successfully used for treatment of multiple sclerosis (MS) and can be combined to increase efficacy. Objective. We used MTX, RTX, and methylprednisolone in a single combined regiment and observed patients prospectively. Methods. We present results of observational pilot study of combined therapy of RTX and MTX in 28 patients with active MS. Therapeutic protocol consisted of two infusions within 14 days. First infusion was 1000 mg methylprednisolone (MP) IV, 1000 mg RTX IV, and 20 mg MTX IV. On day 14, 1000 mg MP IV and 1000 mg RTX IV were given. Patients were followed prospectively from 12 to 48 months. Results and Conclusion. There were no relapses among all 28 patients during the observation period. B-cell depletion of CD19+ and CD19+/CD27+ memory B-cell subpopulation in both compartments was confirmed in all patients at 6 months. We found a more rapid reconstitution of B cells in the CSF than in the peripheral blood and longstanding depression of CD19+CD27+ memory B-cell. Conclusion. Effectiveness of combined regimen of RTX and MTX could be related to longstanding depletion of CD19+CD27+ memory B-cell subset.

B-Cell Depletion and COVID-19 Severity in Multiple Sclerosis: Remaining Challenges

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012754
Author(s):  
Joep Killestein ◽  
Menno M. Schoonheim ◽  
Rhonda R. Voskuhl
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

scholarly journals Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study

2017 ◽  
Vol 25 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Mark A Agius ◽  
Gabriela Klodowska-Duda ◽  
Maciej Maciejowski ◽  
Andrzej Potemkowski ◽  
Jing Li ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Phase 1 ◽  
B Cell Depletion ◽  
Serious Adverse Events ◽  
T2 Lesions ◽  
Subcutaneous Dose ◽  
Dose Study

Background: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells. Objectives: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS. Methods: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19+ B-cell count to ⩾80 cells/µL. Results: Complete B-cell depletion was observed across all doses. Infusion/injection (grade 1/2) reactions occurred in 6/15 patients receiving inebilizumab IV, 2/5 placebo IV and 1/6 inebilizumab SC. Serious adverse events occurred in three patients receiving inebilizumab: pyrexia, mixed-drug intoxication (unrelated to inebilizumab; resulted in death) and urinary tract infection. Mean number of cumulative new gadolinium-enhancing lesions over 24 weeks was 0.1 with inebilizumab versus 1.3 with placebo; mean numbers of new/newly enlarging T2 lesions were 0.4 and 2.4, respectively. Conclusion: Inebilizumab had an acceptable safety profile in relapsing MS patients and showed a trend in reductions in new/newly enlarging and gadolinium-enhancing lesions.

Lung Memory B Cell Populations After Influenza Infection in Mice

2019 ◽  
Author(s):  
M. Breen ◽  
F. Feng ◽  
K. Barker ◽  
A. Hua ◽  
Y.M. Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Influenza Infection ◽  
Cell Populations ◽  
Memory B Cell

scholarly journals B cell depletion can be effective in multiple sclerosis but failed in a patient with advanced childhood cerebral X-linked adrenoleukodystrophy

2019 ◽  
Vol 12 ◽  
pp. 175628641986813
Author(s):  
Hendrik Rosewich ◽  
Stefan Nessler ◽  
Wolfgang Brück ◽  
Jutta Gärtner
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
B Lymphocytes ◽  
Specific Pattern ◽  
B Cell Depletion ◽  
Compassionate Use ◽  
Clinical Imaging ◽  
Relapsing Remitting ◽  
Advanced Stages ◽  
Relapsing Remitting Multiple Sclerosis

Rituximab exerts its clinical efficacy by its specific pattern of depletion of CD20+ B lymphocytes and it has been demonstrated that rituximab is an effective treatment for relapsing remitting multiple sclerosis. X-linked adrenoleukodystrophy (X-ALD), the most common monogenetic neuroinflammatory disorder, shares substantial overlap with multiple sclerosis in the neuropathological changes found in brain tissues in advanced stages of the disease. While there is no effective therapy for these patients, we hypothesized that rituximab might be effective in arresting the neuroinflammatory process. Our detailed clinical, imaging and immunological data revealed that rituximab is not effective in advanced stages of X-ALD and consequently should not be applied for compassionate use in these patients.

scholarly journals Optimisation of ex vivo memory B cell expansion/differentiation for interrogation of rare peripheral memory B cell subset responses

2018 ◽  
Vol 2 ◽  
pp. 97 ◽  
Author(s):  
Luke Muir ◽  
Paul F. McKay ◽  
Velislava N. Petrova ◽  
Oleksiy V. Klymenko ◽  
Sven Kratochvil ◽  
...  
Keyword(s):  
Cell Culture ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
Ex Vivo ◽  
Cell Subset ◽  
Human Memory ◽  
Memory B Cells ◽  
Memory B Cell ◽  
B Cell Subsets

Background:Human memory B cells play a vital role in the long-term protection of the host from pathogenic re-challenge. In recent years the importance of a number of different memory B cell subsets that can be formed in response to vaccination or infection has started to become clear. To study memory B cell responses, cells can be culturedex vivo,allowing for an increase in cell number and activation of these quiescent cells, providing sufficient quantities of each memory subset to enable full investigation of functionality. However, despite numerous papers being published demonstrating bulk memory B cell culture, we could find no literature on optimised conditions for the study of memory B cell subsets, such as IgM+memory B cells.Methods:Following a literature review, we carried out a large screen of memory B cell expansion conditions to identify the combination that induced the highest levels of memory B cell expansion. We subsequently used a novel Design of Experiments approach to finely tune the optimal memory B cell expansion and differentiation conditions for human memory B cell subsets. Finally, we characterised the resultant memory B cell subpopulations by IgH sequencing and flow cytometry.Results:The application of specific optimised conditions induce multiple rounds of memory B cell proliferation equally across Ig isotypes, differentiation of memory B cells to antibody secreting cells, and importantly do not alter the Ig genotype of the stimulated cells. Conclusions:Overall, our data identify a memory B cell culture system that offers a robust platform for investigating the functionality of rare memory B cell subsets to infection and/or vaccination.

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