研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

静脉注射甲基强的松龙对急性期视神经脊髓炎的影响。

Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase.

发表日期:2024 Sep 02
作者: Shengnan Wang, Mengru Xue, Jianglong Wang, Rui Wu, Yanqing Shao, Ke Luo, Jiacheng Liu, Mingqin Zhu
来源: Annals of Clinical and Translational Neurology

摘要:

视神经脊髓炎谱系障碍 (NMOSD) 是一种抗水通道蛋白 4 (抗 AQP4) 自身抗体介导的中枢神经系统特发性炎症性脱髓鞘疾病。虽然静脉脉冲甲基泼尼松龙 (IVMP) 是急性发作 NMOSD 的推荐初始治疗选择,但其治疗机制仍不清楚。我们假设 IVMP 会减少 NMOSD 患者促炎因子的表达并增加炎症的消退。孟德尔随机化 (MR) 分析用于筛选有意义的炎症和消退因子。三种具有逆方差加权 (IVW) 的 MR 方法主要用于识别阳性结果。从41种炎症因子中筛选出白细胞介素(IL)-10、IL-1β、IL-6、C-X-C基序趋化因子配体12(CXCL12)和肿瘤坏死因子相关凋亡诱导配体(TRAIL),以及resolvin D1(RvD1)从 6 个分辨率标记中筛选出 、maresin 1 (MaR1) 和 lipoxin A4 (LXA4) 以进行包含。随后,12 名 NMOSD 患者入组并接受 IVMP 治疗。在 IVMP 治疗前后通过酶联免疫吸附测定法测量上述炎症和消退标志物的血清水平。高水平的 TRAIL、CXCL12 和 IL-1β 与 NMOSD 风险增加相关(TRAIL:比值比 [OR] ,1.582;95% CI,1.003-2.495;CXCL12:OR,3.610;95% CI,1.011-12.889;IL-1β:OR,4.500;高水平的 RvD1、MaR1 和 LXA4 与 NMOSD 风险降低相关(RvD1:OR,0.725;95% CI,0.538-0.976;MaR1:OR,0.985;95% CI,0.970-0.999;LXA4:OR, 0.849;95% CI,0.727-0.993)。在NMOSD患者中,与治疗前水平相比,IVMP治疗后血清IL-6、CXCL12和TRAIL水平显着降低,而IL-1β、LXA4和MaR1水平在IVMP治疗后显着升高(p<<0.05)。 CXCL12水平与扩展残疾状态量表(EDSS)评分之间观察到显着正相关(r = 0.451,p < 0.05)。确定了与NMOSD发病机制相关的几种全身炎症调节因子。 LXA4和MaR1的保护作用可能是糖皮质激素治疗中不可或缺的组成部分。因此,使用解析标记可能是改善 NMOSD 个体中枢神经系统损伤的潜在策略。© 2024 作者。 《临床和转化神经病学年鉴》由 Wiley periodicals LLC 代表美国神经病学协会出版。
Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD.Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment.High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1β: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05).Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.