EBI2-expressing B cells in neuromyelitis optica spectrum disorder with AQP4-IgG: Association with acute attacks and serum cytokines

2021 ◽  
pp. 577637
Author(s):  
Seol-Hee Baek ◽  
Boram Kim ◽  
Je-Young Shin ◽  
Seok-Jin Choi ◽  
So Hyun Ahn ◽  
...  
Keyword(s):  
B Cells ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Serum Cytokines ◽  
Acute Attacks

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.

The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder

2018 ◽  
Vol 39 (3) ◽  
pp. 543-549 ◽  
Author(s):  
Eun Bin Cho ◽  
Hye-Jin Cho ◽  
Jin Myoung Seok ◽  
Ju-Hong Min ◽  
Eun-Suk Kang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Neuromyelitis Optica ◽  
Regulatory T Cell ◽  
Spectrum Disorder ◽  
T Cell Subsets ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Regulatory B Cells ◽  
B10 Cells

scholarly journals Effects of Vitamin D and Dexamethasone on Lymphocyte Proportions and Their Associations With Serum Concentrations of 25-Hydroxyvitamin D3In Vitro in Patients With Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Eun Bin Cho ◽  
Jong Hwa Shin ◽  
Soonwook Kwon ◽  
Juhyeon Kim ◽  
Jin Myoung Seok ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
B Cells ◽  
Neuromyelitis Optica ◽  
Active Form ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Serum Concentrations ◽  
The Impact ◽  
Stimulation Of

BackgroundClear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate.Objective and MethodsPatients with MS (N=12) and neuromyelitis optica spectrum disorder (NMOSD; N=12) were enrolled along with 15 healthy controls. Changes in lymphocyte subset proportions during stimulation of their peripheral blood mononuclear cells (PBMCs) with the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and correlations with serum concentrations of the vitamin D precursor 25-hydroxyvitamin D3 (serum 25(OH)D3) were explored. The impact of 1,25(OH)2D3 stimulation on the expression of vitamin-D-responsive genes in immune cells was also investigated.ResultsIn both MS and NMOSD, stimulation of PBMCs with 1,25(OH)2D3 followed by steroid suppressed the proliferation of total lymphocytes and T cells. The ratio of CD19+CD27+ memory B cells (Bmem) to all B cells after stimulation with 1,25(OH)2D3 was negatively correlated with serum 25(OH)D3 in MS (Spearman’s ρ=–0.594, p=0.042), but positively correlated in NMOSD (Pearson’s r = 0.739, p=0.006). However, there was no relationship between the ratio of Bmem to CD19+CD24+CD38+ regulatory B cells and serum 25(OH)D3 in either MS or NMOSD. In addition, the level of 1,25(OH)2D3-induced CYP24A1 mRNA expression in PBMCs was significantly and negatively correlated with serum 25(OH)D3 (for ΔCT, r=0.744, p=0.014) in MS.ConclusionThese findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D3 and the proportion of Bmem under immune-cell stimulation differed between MS and NMOSD. Further investigations are warranted with larger patient populations.

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.

Sign in / Sign up

Export Citation Format

Share Document