Lymphocyte Subsets Are Associated with Disease Status in Neuromyelitis Optica Spectrum Disorders

2021 ◽  
pp. 1-10
Author(s):  
Hong Yang ◽  
Wei Liu ◽  
Yi-Fan Wu ◽  
De-Sheng Zhu ◽  
Xia-Feng Shen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
B Cells ◽  
Neuromyelitis Optica ◽  
Peripheral Blood ◽  
Lymphocyte Subsets ◽  
Disease Status ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Spinal Cord Lesions ◽  
Cross Sectional ◽  
Spectrum Disorders

<b><i>Objective:</i></b> At present, studies on lymphocytes are mostly conducted on CD19<sup>+</sup> B cells and CD27<sup>+</sup> B cells in neuromyelitis optica spectrum disorders (NMOSDs), but the exact changes in lymphocyte subsets (CD19<sup>+</sup> B cells, CD3<sup>+</sup> T cells, CD4<sup>+</sup> Th cells, CD8<sup>+</sup> Ts cells, the CD4<sup>+</sup>/CD8<sup>+</sup> ratio, and NK [CD56+ CD16] cells) have rarely been studied. This study aimed to assess lymphocyte subset changes in patients with NMOSD. <b><i>Methods:</i></b> We performed a cross-sectional study of consecutive patients with acute NMOSD (<i>n</i> = 41), chronic NMOSD (<i>n</i> = 21), and healthy individuals (<i>n</i> = 44). Peripheral blood samples were obtained upon admission, and lymphocyte subsets were analyzed by flow cytometry. Levels of lymphocyte subsets among 3 groups were compared and its correlation with the length of spinal cord lesions was analyzed. <b><i>Results:</i></b> The levels of peripheral blood CD19<sup>+</sup> B cells were significantly higher in patients with acute and chronic NMOSD than in healthy controls (HCs) (17.91 ± 8.7%, 13.08 ± 7.562%, and 12.48 ± 3.575%, respectively; <i>p</i> &#x3c; 0.001) and were positively correlated with the length of spinal cord lesions in acute NMOSD (<i>r</i> = 0.433, <i>p</i> &#x3c; 0.05). The peripheral blood CD4<sup>+</sup>/CD8<sup>+</sup> ratio was significantly lower in patients with acute NMOSD and chronic NMOSD than in HCs (1.497 ± 0.6387, 1.33 ± 0.5574, and 1.753 ± 0.659, respectively; <i>p</i> &#x3c; 0.05), and the levels of peripheral blood NK (CD56+ CD16) cells were significantly lower in patients with acute and chronic NMOSD than in HCs (13.6 ± 10.13, 11.11 ± 7.057, and 14.7 [interquartile range = 9.28], respectively; <i>p</i> &#x3c; 0.01). <b><i>Conclusions:</i></b> The levels of certain subsets of peripheral blood lymphocytes are associated with disease status in NMOSD.

Ring-enhancing spinal cord lesions in neuromyelitis optica spectrum disorders

2016 ◽  
Vol 88 (3) ◽  
pp. 218-225 ◽  
Author(s):  
Nicholas L Zalewski ◽  
Padraig P Morris ◽  
Brian G Weinshenker ◽  
Claudia F Lucchinetti ◽  
Yong Guo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Spinal Cord Lesions ◽  
Spectrum Disorders

scholarly journals Spinal cord involvement in multiple sclerosis and neuromyelitis optica spectrum disorders

2019 ◽  
Vol 18 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Olga Ciccarelli ◽  
Jeffrey A Cohen ◽  
Stephen C Reingold ◽  
Brian G Weinshenker ◽  
Maria Pia Amato ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Spinal Cord Involvement ◽  
Spectrum Disorders

scholarly journals Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders.

2020 ◽  
Author(s):  
Leung-Wah Yick ◽  
Chi-Ho Tang ◽  
Oscar Ka-Fai Ma ◽  
Jason Shing-Cheong Kwan ◽  
Koon Ho CHAN
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neurotrophic Factor ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Glutamate Excitotoxicity ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Motor Impairments ◽  
Spectrum Disorders

Abstract Background: Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG. Methods: Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA. Results: Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.

scholarly journals Pharmacodynamic modeling and exposure-response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders

2021 ◽  
Author(s):  
Li Yan ◽  
Bing Wang ◽  
Dewei She ◽  
Ben Mitchel ◽  
Ryan Criste ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Drug Exposure ◽  
Response Assessment ◽  
Pharmacodynamic Modeling ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Spectrum Disorders ◽  
Disease Attack ◽  
The Impact

AIM: Neuromyelitis optica spectrum disorders (NMOSD) is an autoantibody-mediated, B cell-driven disease. Inebilizumab is a humanized, affinity-optimized, afucosylated IgG1 kappa monoclonal antibody that binds to the B cell specific surface antigen CD19, resulting in rapid, profound, and sustained depletion of circulating peripheral B cells in NMOSD subjects (pivotal study). The objective of this study was to conduct population modeling of B cell response following inebilizumab treatment in adult subjects with NMOSD, and to assess the impact of drug exposure to outcome. METHODS: A hematopoietic transit model was developed to describe the joint effects of reducing influx from pro-B cells and accelerating CD20+ B cell depletion in the blood by inebilizumab. Furthermore, the relationships between inebilizumab pharmacokinetic (PK) exposure and the primary efficacy endpoint and key secondary efficacy endpoints were evaluated. KEY RESULTS: At the 300 mg dose, there was no apparent relationship between efficacy (reduction in disease attack risk, risk of worsening from baseline in Expanded Disability Status Scale, cumulative total active MRI lesions, and the number of NMOSD-related in-patient hospitalizations) and PK exposure. Subjects with low, medium, and high PK exposure had a similar hazard ratio of NMOSD attack vs placebo group. CONCLUSIONS: The pharmacodynamic modeling confirmed effective depletion of B cells is achieved with a 300 mg intravenous dose of inebilizumab administered on Day 1 and Day 15 and every 6 months thereafter. The PK variability between patients had no apparent effect on clinical efficacy.

Spinal Cord Atrophy in Neuromyelitis Optica Spectrum Disorders Is Spatially Related to Cord Lesions and Disability

Radiology ◽  
2020 ◽  
Vol 297 (1) ◽  
pp. 154-163
Author(s):  
Laura Cacciaguerra ◽  
Paola Valsasina ◽  
Sarlota Mesaros ◽  
Vittorio Martinelli ◽  
Jelena Drulovic ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Spinal Cord Atrophy ◽  
Spectrum Disorders
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