Functional impairment of CD19 + CD24 hi CD38 hi B cells in neuromyelitis optica spectrum disorder is restored by B cell depletion therapy

2021 ◽  
Vol 13 (624) ◽  
Author(s):  
Yeseul Kim ◽  
So Yeon Kim ◽  
Sang-Min Han ◽  
Rosah May Payumo ◽  
Kevin Park ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Functional Impairment ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder

Prolonged B-cell depletion after rituximab in AQP4-IgG-positive neuromyelitis optica spectrum disorder

2021 ◽  
pp. 577666
Author(s):  
Elia Sechi ◽  
Roberto Zarbo ◽  
Maria Angela Biancu ◽  
Paola Chessa ◽  
Maria Laura Idda ◽  
...  
Keyword(s):  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder

scholarly journals Use of B-Cell–Depleting Therapy in Women of Childbearing Potential With Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

2022 ◽  
pp. 10.1212/CPJ.0000000000001147
Author(s):  
Alexandra Galati ◽  
Thomas McElrath ◽  
Riley Bove
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Childbearing Potential ◽  
Pregnancy And Postpartum

AbstractPurposeof Review: There is considerable heterogeneity in the use of B cell depletion in women of childbearing age, likely driven at least in part by the discrepancy between the product labels and what is known about the physiology of IgG1, including breastmilk and placental transfer.Recent Findings:We provide practical considerations on the use of this medication class in women of childbearing potential. We discuss pre-pregnancy planning including vaccinations, safety of B cell depletion during pregnancy as well as postpartum considerations including breastfeeding.Summary:B cell depleting monoclonal antibodies have shown to be effective for pre-pregnancy and postpartum prevention of inflammatory activity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). B cell depleting therapies are large IgG1 monoclonal antibodies which have minimal transfer across the placenta and into breastmilk. Consideration of risks and benefits of these therapies should be considered in counseling women planning pregnancy and postpartum.

scholarly journals Two Cases of Pediatric AQP4-Antibody Positive Neuromyelitis Optica Spectrum Disorder Successfully Treated with Tocilizumab

2019 ◽  
Vol 50 (03) ◽  
pp. 193-196
Author(s):  
Markus Breu ◽  
Sarah Glatter ◽  
Romana Höftberger ◽  
Michael Freilinger ◽  
Karl Kircher ◽  
...  
Keyword(s):  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Interleukin 6 Receptor ◽  
Anti Cd20 ◽  
Aqp4 Antibody

AbstractB cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.

scholarly journals CNS Aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder

2017 ◽  
Vol 4 (6) ◽  
pp. 369-380 ◽  
Author(s):  
Markus C. Kowarik ◽  
David Astling ◽  
Christiane Gasperi ◽  
Scott Wemlinger ◽  
Hannah Schumann ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Aquaporin 4 ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Cell Compartments

scholarly journals Effects of Tocilizumab Therapy on Circulating B Cells and T Helper Cells in Patients With Neuromyelitis Optica Spectrum Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Ye Liu ◽  
Huiming Zhang ◽  
Tian-Xiang Zhang ◽  
Meng Yuan ◽  
Chen Du ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Memory B Cells ◽  
Spectrum Disorder ◽  
Significant Shift ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
T Helper ◽  
Color Flow

Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, showed its therapeutic efficacy on neuromyelitis optica spectrum disorder (NMOSD). To assess the immunological effects of this drug on B cells, follicular T helper (Tfh) cells, and peripheral T helper (Tph) cells in patients with NMOSD, peripheral B cell and Tfh cell phenotypes were evaluated in 26 patients with NMOSD before and after tocilizumab treatment by nine-color flow cytometry, as well as the expression of costimulatory and co-inhibitory molecules on B cells. Results showed that the frequency of CD27+IgD− switched memory B cells, CD27-IgD- double-negative B cells, and CD27highCD38high antibody-secreting cells was increased in patients with NMOSD. Tocilizumab treatment led to a significant shift of B cells to naïve B cells from memory B cells after 3 months. Three markers on B cells associated with T-cell activation (i.e., CD86 CD69, and HLA-DR) were downregulated after tocilizumab treatment. The frequencies of total Tfh and Tph cells were decreased, whereas that of follicular regulatory T cells tended to increase. Intrinsic increased PD-L1 and PD-L2 expression was characteristic of B cells in patients with NMOSD. Tocilizumab selectively restored PD-L1 on B-cell subsets. These results provided evidence that tocilizumab enhanced B- and T-cell homoeostasis by regulating B-cell differentiation and inhibiting lymphocyte activation in patients with NMOSD.

scholarly journals Dysregulated B cell differentiation towards antibody-secreting cells in neuromyelitis optica spectrum disorder

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yasunobu Hoshino ◽  
Daisuke Noto ◽  
Shuhei Sano ◽  
Yuji Tomizawa ◽  
Kazumasa Yokoyama ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Transcriptome Analysis ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
B Cell Differentiation ◽  
B Cell Subsets ◽  
Multiple Sclerosis Patients ◽  
Antibody Secreting Cells

Abstract Background Anti-aquaporin 4 (AQP4) antibody (AQP4-Ab) is involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). However, the mechanism involved in AQP4-Ab production remains unclear. Methods We analyzed the immunophenotypes of patients with NMOSD and other neuroinflammatory diseases as well as healthy controls (HC) using flow cytometry. Transcriptome analysis of B cell subsets obtained from NMOSD patients and HCs was performed. The differentiation capacity of B cell subsets into antibody-secreting cells was analyzed. Results The frequencies of switched memory B (SMB) cells and plasmablasts were increased and that of naïve B cells was decreased in NMOSD patients compared with relapsing–remitting multiple sclerosis patients and HC. SMB cells from NMOSD patients had an enhanced potential to differentiate into antibody-secreting cells when cocultured with T peripheral helper cells. Transcriptome analysis revealed that the profiles of B cell lineage transcription factors in NMOSD were skewed towards antibody-secreting cells and that IL-2 signaling was upregulated, particularly in naïve B cells. Naïve B cells expressing CD25, a receptor of IL-2, were increased in NMOSD patients and had a higher potential to differentiate into antibody-secreting cells, suggesting CD25+ naïve B cells are committed to differentiate into antibody-secreting cells. Conclusions To the best of our knowledge, this is the first study to demonstrate that B cells in NMOSD patients are abnormally skewed towards antibody-secreting cells at the transcriptome level during the early differentiation phase, and that IL-2 might participate in this pathogenic process. Our study indicates that CD25+ naïve B cells are a novel candidate precursor of antibody-secreting cells in autoimmune diseases.

scholarly journals B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asuka Tanaka ◽  
Kentaro Ide ◽  
Yuka Tanaka ◽  
Masahiro Ohira ◽  
Hiroyuki Tahara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Anti Cd20

AbstractPretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+ T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+ T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+ T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+ T cell response. The depletion of the CD5+ B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+ CD5+ B cells suppress the excessive response of anti-donor CD4+ T cells responses in sensitized recipients.

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