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 ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Ye Liu ◽  
Huiming Zhang ◽  
Tian-Xiang Zhang ◽  
Meng Yuan ◽  
Chen Du ◽  
...  

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.


2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yasunobu Hoshino ◽  
Daisuke Noto ◽  
Shuhei Sano ◽  
Yuji Tomizawa ◽  
Kazumasa Yokoyama ◽  
...  

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.


2017 ◽  
Vol 23 (14) ◽  
pp. 1950-1954 ◽  
Author(s):  
Jinhua Zhang ◽  
Fang Liu ◽  
Yiqi Wang ◽  
Ying Yang ◽  
Yuehong Huang ◽  
...  

Understanding the characteristics of neuromyelitis optica spectrum disorder (NMOSD) with recurrent short partial transverse myelitis (SPTM), which is very rare, contributes to the differential diagnosis of multiple sclerosis (MS). We present two Chinese aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD cases who had at least twice SPTM during 4 and 6 years of follow-up, respectively. Their SPTMs have been mild and responded well to corticosteroids just like in the case of MS. The findings highlight the need of searching for serum AQP4-IgG (cell-based assay strongly recommended) in patients with recurrent SPTM and suggest that those patients may have a mild acute attack phase and favorable long-term prognosis.


2011 ◽  
Vol 18 (2) ◽  
pp. 244-247 ◽  
Author(s):  
Sung-Min Kim ◽  
Ji-Soo Kim ◽  
Young Eun Heo ◽  
Hye-Ran Yang ◽  
Kyung Seok Park

Neuromyelitis optica (NMO), mainly affecting optic nerve and spinal cord, can also manifest diverse ocular symptoms due to brain abnormalities. We present a cortical oscillopsia without nystagmus or head tremor in a patient with neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin 4 antibody. This rare ocular manifestation, which is easily underestimated owing to absence of the typical nystagmus, can be an initial manifestation of NMOSD.


2021 ◽  
pp. 577666
Author(s):  
Elia Sechi ◽  
Roberto Zarbo ◽  
Maria Angela Biancu ◽  
Paola Chessa ◽  
Maria Laura Idda ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
pp. 10-16
Author(s):  
Vahid Shaygannejad ◽  
◽  
Mahdi Barzegar ◽  
Navid Manouchehri ◽  
Nafiseh Esmaeil ◽  
...  

Background: The absence of Aquaporin-4 Antibody (AQP4-Ab) in a fraction of the Neuromyelitis Optica Spectrum Disorder (NMOSD) patients has led to a search for other serologic markers. Myelin Oligodendrocyte Glycoprotein (MOG) is a protein component of the myelin sheets encapsulating the neural fibers. Objectives: We aimed to compare the presence and levels of anti-MOG (Ig-G) in a group of seronegative NMOSD patients with a healthy control group. Materials & Methods: In this cross-sectional study, 30 NMOSD patients with negative AQP-Ab status, who were referred to the Neurology Clinic of Kashani University Hospital in Isfahan City, Iran, from March 2015 to March 2016, and 26 healthy controls were consecutively recruited. Their baseline demographic and clinical data were recorded. Serum anti-MOG levels were measured in both groups. The obtained data were analyzed using the Student t-test, Mann-Whitney U, and Chisquare test in SPSS V. 18. Results: The anti-MOG test results were statistically higher in patients (n=12, 37.5%) compared to controls (n=0, 0%) (P<0.0001). The level of anti-MOG in Healthy Control (HC) was higher compared to patients with negative anti-MOG (P<0.0001) and was lower than patients with positive anti-MOG (P<0.0001). Conclusion: Our study showed that nearly one-third of seronegative NMOSD patients were positive for MOG-Ab. Further studies are needed to assess the characteristics and outcome of these patients.


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