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

OBJECTIVE: At present, studies on lymphocytes are mostly conducted on CD19+ B cells and CD27+ B cells in neuromyelitis optica spectrum disorders (NMOSDs), but the exact changes in lymphocyte subsets (CD19+ B cells, CD3+ T cells, CD4+ Th cells, CD8+ Ts cells, the CD4+/CD8+ ratio, and NK [CD56+ CD16] cells) have rarely been studied. This study aimed to assess lymphocyte subset changes in patients with NMOSD. METHODS: We performed a cross-sectional study of consecutive patients with acute NMOSD (n = 41), chronic NMOSD (n = 21), and healthy individuals (n = 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. RESULTS: The levels of peripheral blood CD19+ 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; p < 0.001) and were positively correlated with the length of spinal cord lesions in acute NMOSD (r = 0.433, p < 0.05). The peripheral blood CD4+/CD8+ 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; p < 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; p < 0.01). CONCLUSIONS: The levels of certain subsets of peripheral blood lymphocytes are associated with disease status in NMOSD.

Comprehensive Analysis of N6-Methyladenosine (m6A) Methylation in Neuromyelitis Optica Spectrum Disorders.

Background: N6-Methyladenosine (m6A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known. Aims: To explore the mechanism of m6A in NMOSD patients. Methods: This study assessed the m6A methylation levels in blood from two groups: NMOSD patients and healthy controls. Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA-seq were performed to assess differences in m6A methylation between NMOSD patients and healthy controls. Ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS) method was performed to check m6A level. Differential m6A methylation genes were validated by MeRIP-qPCR. Results: Compared with that in the control group, the total m6A level was decreased in the NMOSD group. Genes with upregulated methylation were primarily enriched in processes associated with RNA splicing, mRNA processing, and innate immune response, while genes with downregulated methylation were enriched in processes associated with the regulation of transcription, DNA-templating, and the positive regulation of I-kappa B kinase/NF-kappa B signalling. Conclusion: These findings demonstrate that differential m6A methylation may act on functional genes to regulate immune homeostasis in NMOSD.

Lower serum interleukin-22 and interleukin-35 levels are associated with disease status in neuromyelitis optica spectrum disorders.

AIMS: The exact pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) remains unclear. A variety of cytokines are involved, but few studies have been performed to explore the novel roles of interleukin-22 (IL-22) and interleukin-35 (IL-35) in NMOSD. Therefore, this study was designed to investigate serum levels of IL-22 and IL-35, and their correlations with clinical and laboratory characteristics in NMOSD. METHODS: We performed a cross-section study, 18 patients with acute NMOSD, 23 patients with remission NMOSD, and 36 healthy controls were consecutively enrolled. Serum levels of IL-22 and IL-35 were measured by enzyme-linked immunosorbent assay (ELISA). The correlations between serum IL-22 and IL-35 levels and clinical and laboratory characteristics were evaluated by Spearman's rank or Pearson's correlation coefficient. RESULTS: The serum levels of IL-22 and IL-35 were significantly lower in patients with acute NMOSD and remission NMOSD than in healthy controls (IL-22: 76.96 ± 13.62 pg/mL, 87.30 ± 12.79 pg/mL, and 94.02 ± 8.52 pg/mL, respectively, P < .0001; IL-35: 45.52 ± 7.04 pg/mL, 57.07 ± 7.68 pg/mL, and 60.05 ± 20.181 pg/mL, respectively, P < .0001). Serum levels of IL-35 were negatively correlated with EDSS scores and cerebrospinal fluid protein levels (r = -.5438, P = .0002 and r = -.3523, P = .0258, respectively) in all patients. CONCLUSIONS: Lower serum levels of IL-22 and IL-35 are associated with disease status in NMOSD. Additionally, lower serum levels of IL-35 are associated with disease severity in NMOSD.