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Currently, no data are available regarding the expression levels of CD40L on CD4 + T cells in patients with neuromyelitis optica spectrum disorders (NMOSD). The percentage of circulating CD40L + CD4 + T cells was measured by flow cytometry in 23 NMOSD patients and 10 healthy controls. The ratio of CD40L + CD4 + to CD4 + T cells in patients at acute phase (18.28 ± 15.56%) was significantly higher than that in healthy controls (7.23 ± 5.94%, P = .032) and was positively correlated with disease severity (r = 0.532, P = .041). Thus, our results suggest an important role of this molecule in acute attacks of NMOSD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene encodes a vital co-stimulatory molecule of the immune system and has been identified as a susceptibility locus for systemic lupus erythematosus, systemic sclerosis, and primary Sjögren's syndrome. However, the association of TNFSF4 polymorphisms with neuromyelitis optica spectrum disorders (NMOSD), an inflammatory, demyelinating autoimmune disease of the central nervous system, has not yet been investigated. To evaluate whether TNFSF4 polymorphisms contribute to risk of NMOSD, four single-nucleotide polymorphisms (SNPs) (rs1234315, rs2205960, rs704840, and rs844648) were selected and genotyped in a cohort of 312 patients with NMOSD and 487 healthy controls. Our study showed that rs844648 was associated with an increased risk of NMOSD, according to the allelic model (OR = 1.30, 95% CI 1.06-1.59, P = 0.011, Pcorr = 0.044). Significant associations of rs844648 (OR = 1.67, 95% CI 1.17-2.38, P = 0.005, Pcorr = 0.02) and rs704840 (OR = 1.75, 95% CI 1.17-2.63, P = 0.007, Pcorr = 0.027) with NMOSD occurrence were also observed under the recessive model. Moreover, linkage disequilibrium analysis revealed two blocks within TNFSF4; in one block, the haplotype A rs844648 G rs704840 significantly increased the risk of NMOSD, whereas G rs844648 T rs704840 reduced the risk. This study demonstrates an association between TNFSF4 polymorphisms and susceptibility for the development of NMOSD in the Chinese population.

STAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case-control study to determine whether STAT4 contributed to the risk of NMOSD. We tested five STAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to identify associations with NMOSD. The results of multiple test comparisons were corrected using the Benjamini and Hochberg false discovery rate (FDR-BH). After correcting for multiple test comparisons, the minor alleles of four STAT4 SNPs exhibited significant association with increased risk of NMOSD (rs7574865 T, odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.32-2.08, P corr  = 0.000; rs10181656 G, OR = 1.62, 95% CI 1.29-2.03, P corr  = 0.000; rs10168266 T, OR = 1.59, 95% CI 1.27-2.00, P corr  = 0.001; and rs13426947 A, OR = 1.51, 95% CI 1.21-1.90, P corr  = 0.004). Identical results were observed in the dominant, recessive, and additive models. In contrast, the G allele of rs7601754 displayed a protective effect against NMOSD (OR = 0.53, 95% CI 0.36-0.76, P corr  = 0.006). Our study indicates that STAT4 polymorphisms are associated with the risk of NMOSD, which provides novel insights into the underlying mechanisms of this disease.

Background: Painful tonic spasm (PTS) is a common symptom in patients with neuromyelitis optica spectrum disorders (NMOSD). This study aimed to obtain further insights into the prevalence, characteristics, and treatment of PTS in patients with NMOSD, and to systematically investigate and compare the clinical features and prognosis of NMOSD with and without PTS., Methods: We reviewed the medical records and prospectively interviewed patients with NMOSD who attended the West China Hospital of Sichuan University in Chengdu, China between September 2014 and December 2016., Results: In total, 52 of the 230 patients with NMOSD experienced PTS (22.61%). Patients with NMOSD and PTS were characterized by a higher age at onset (P = 0.017), higher annual relapse rate (ARR) (P = 0.003), higher ARR of myelitis (P = 0.011), and a tendency to experience pruritus (P = 0.025). Sodium channel blocking antiepileptic drugs (carbamazepine or oxcarbazepine) had higher efficacy than gabapentin in the treatment of PTS (P = 0.001). Although the progression index was higher in patients with PTS, this difference did not reach statistical significance (P = 0.05)., Conclusions: Our study suggested that immunosuppressors for the prevention of relapse should be administered without delay in patients with NMOSD and PTS. Owing to the side effects of carbamazepine, we recommend oxcarbazepine as the first-line of treatment for PTS in patients with NMOSD. Whether PTS is a marker of disease severity in NMOSD remains to be determined, requiring a long-term prospective observational study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The CD40 gene is associated with many autoimmune diseases; however, there are few studies in literatures that investigate the association between CD40 and neuromyelitis optica spectrum disorders (NMOSD). This study aimed to estimate the potential association of CD40 gene polymorphisms with susceptibility to NMOSD. Four SNPs (rs1883832, rs3765459, rs4810485, and rs6074022) were selected and genotyped in a Chinese cohort comprising 162 patients with NMOSD and 237 healthy controls. P values, odds ratios (ORs), and 95 % confidential intervals (CI) for four test models (allelic, additive, dominant, and recessive) were used to assess relationships between CD40 and NMOSD. Results showed that the rs3765459 variant was significantly associated with increased risk of NMOSD in allelic model (OR = 1.48, 95 % CI 1.10-1.98, P = 0.009, P corr  = 0.037), and similar results were detected in the additive and recessive models (OR = 1.47, 95 % CI 1.09-1.97, P = 0.010, P corr  = 0.042; OR = 2.12, 95 % CI 1.18-3.8, P = 0.012, P corr  = 0.048, respectively). Other three SNPs showed protections on NMOSD in dominant models (rs6074022, OR = 0.64, 95 % CI 0.42-0.95, P = 0.031; rs1883832, OR = 0.65, 95 % CI 0.43-0.97, P = 0.036; and rs4810485, OR = 0.63, 95 % CI 0.42-0.95, P = 0.029, respectively), but not significantly after Bonferroni corrections for multiple tests. In addition, haplotype analysis of these SNPs in tight linkage did not reveal significant association with NMOSD. This study indicates that the rs3765459 variant in CD40 gene is associated with susceptibility to NMOSD. Larger sample size studies in other ethnicities are needed to verify this association.

This study aimed to perform a comprehensive assessment of the association between CD58 polymorphisms and the risk of neuromyelitis optica spectrum disorders (NMOSD) in a Han Chinese population. Nine single-nucleotide polymorphisms (SNPs) were genotyped in 230 NMOSD patients and 487 healthy controls. Five SNPs were significantly associated with an increased risk of NMOSD (rs2300747, rs1335532, rs56302466, rs1016140, and rs12044852). The haplotype TAGCCCAA significantly increased the risk of NMOSD, while TATTACGG reduced the risk. In conclusion, this study identified a new NMOSD susceptibility variant, rs56302466, and suggested that CD58 polymorphisms are associated with the risk of NMOSD in Han Chinese., (Copyright © 2017. Published by Elsevier B.V.)