炎症谱与肌萎缩侧索硬化症各亚型的生存相关。
Inflammatory profiles relate to survival in subtypes of amyotrophic lateral sclerosis.
机构信息
From the Institutes of Regional Health Research and Molecular Medicine (M.N.O., N.A.), University of Southern Denmark; Departments of Neurology (M.N.O.), Slagelse Hospital & Biochemistry & Immunology, Lillebaelt Hospital, Vejle, Denmark; Department of Pharmacology and Clinical Neuroscience (A.W., K.F., P.M.A.), Umeå University, Sweden; Department of Clinical Immunology (A.C.N., S.T.L.), Odense University Hospital, Denmark; Department of Pathology (M.W.), Odense University Hospital, Denmark; Biochemistry & Immunology (J.S.M., I.B.), Lillebaelt Hospital, Vejle, Denmark; Institute of Regional Health Research (J.S.M., I.B.), University of Southern Denmark, Odense; Department of Neurology (N.A.), Slagelse Hospital; and OPEN, Odense Patient Data Explorative Network (N.A.), Odense University Hospital, Denmark.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2020 Mar 2;7(3). doi: 10.1212/NXI.0000000000000697. Print 2020 May.
OBJECTIVE
To investigate inflammatory cytokines in patients with motor neuron disease (MND) evaluating the putative contribution of amyotrophic lateral sclerosis (ALS)-causing gene variants.
METHODS
This study is a retrospective case series with prospective follow-up (1994-2016) of 248 patients with MND, of whom 164 had ALS who were screened for mutations in the genes for and . Paired CSF and plasma were collected at the diagnostic evaluation before treatment. A panel of cytokines were measured blindly via digital ELISA on the Simoa platform.
RESULTS
Time from disease onset to death was longer for patients with ALS-causing mutations (mSOD1, n = 24) than those with hexanucleotide repeat expansion (C9orf72HRE) ALS (n = 19; = 0.001) and other ALS (OALS) (n = 119; = 0.0008). Patients with OALS had higher CSF tumor necrosis factor alpha (TNF-α) compared with those with C9orf72HRE ALS ( = 0.014). Patients with C9orf72HRE ALS had higher CSF interferon alpha compared with those with OALS and mSOD1 ALS ( = 0.042 and = 0.042). In patients with ALS, the survival was negatively correlated with plasma interleukin (IL) 10 (hazard ratio [HR] 1.17, 95% CI 1.05-1.30). Plasma TNF-α, IL-10, and TNF-related apoptosis-inducing ligand (TRAIL) (HR 1.01 [1.00-1.02], 1.15 [1.02-1.30], and 1.01 [1.00-1.01], respectively) of patients with OALS, plasma IL-1β (HR 5.90 [1.27-27.5]) of patients with C9orf72HRE ALS, and CSF TRAIL (10.5 [1.12-98.6]) of patients with mSOD1 ALS all correlated negatively with survival.
CONCLUSIONS
Differences in survival times in ALS subtypes were correlated with cytokine levels, suggesting specific immune responses related to ALS genetic variants.
目的
研究肌萎缩侧索硬化症（ALS）致病基因变异患者的炎症细胞因子，评估其潜在作用。
方法
这是一项回顾性病例系列研究，对 1994 年至 2016 年期间 248 例肌萎缩侧索硬化症（ALS）患者进行前瞻性随访。其中 164 例为 ALS 患者，筛选出 和 基因突变。在治疗前的诊断评估时，收集配对的 CSF 和血浆。使用 Simoa 平台上的数字 ELISA 盲法检测一组细胞因子。
结果
与 C9orf72 六核苷酸重复扩展（C9orf72HRE）ALS 患者（n=19； = 0.001）和其他 ALS（OALS）患者（n=119； = 0.0008）相比，携带 ALS 致病 突变（mSOD1，n=24）的患者从发病到死亡的时间更长。与 OALS 患者相比，C9orf72HRE ALS 患者的 CSF 肿瘤坏死因子-α（TNF-α）水平更高（ = 0.014）。与 OALS 和 mSOD1 ALS 患者相比，C9orf72HRE ALS 患者的 CSF 干扰素-α水平更高（ = 0.042 和 = 0.042）。在 ALS 患者中，血浆白细胞介素（IL）10 与生存呈负相关（风险比 [HR]1.17，95%置信区间 1.05-1.30）。OALS 患者的血浆 TNF-α、IL-10 和 TNF 相关凋亡诱导配体（TRAIL）（HR 分别为 1.01 [1.00-1.02]、1.15 [1.02-1.30]和 1.01 [1.00-1.01]），C9orf72HRE ALS 患者的血浆 IL-1β（HR 5.90 [1.27-27.5]）和 mSOD1 ALS 患者的 CSF TRAIL（HR 10.5 [1.12-98.6]）均与生存呈负相关。
结论
不同 ALS 亚型的生存时间差异与细胞因子水平相关，提示与 ALS 遗传变异相关的特定免疫反应。
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