NLRP3 level in cerebrospinal fluid of patients with neuromyelitis optica spectrum disorders: Increased levels and association with disease severity
NLRP3 level in cerebrospinal fluid of patients with neuromyelitis optica spectrum disorders: Increased levels and association with disease severity
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视神经脊髓炎谱系疾病患者脑脊液中 NLRP3 水平：水平升高及其与疾病严重程度的关联
DOI：
10.1016/j.msard.2019.101888
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Wang Honghao
中科院分区：
文献类型：
--
作者：
Peng Y;Chen Jinyu;Dai Yongqiang;Jiang Ying;Qiu Wei;Gu Yong;Wang Honghao
视神经脊髓炎（NMOSD）和多发性硬化症是最常见的中枢神经系统自身免疫性炎症性脱髓鞘疾病。然而，其发病机制尚不清楚。核苷酸结合富亮氨酸重复序列（NLR）家族pyrin domain containing 3 （NLRP3）是先天免疫系统中由线粒体DNA （mtDNA）激活的重要蛋白，已被报道与多种自身免疫性疾病有关。目的观察NMOSD和MS患者脑脊液NLRP3、mtDNA及炎症相关细胞因子（IL-1β、IL-6、IL-17）水平的变化，并探讨这些因素之间的相关性。方法选取NMOSD患者28例，MS患者15例，非炎性神经系统疾病对照组16例。ELISA法检测NLRP3炎性体、IL-1β、IL-6、IL-17。采用qPCR检测脑脊液细胞外mtDNA。采用EDSS评分评价临床表现的严重程度。结果NMOSD患者scsf中NLRP3、mtDNA、IL-1β、IL-6、IL-17水平均高于对照组。与对照组相比，MS患者脑脊液NLRP3、mtDNA和IL-6升高。NMOSD患者CSF NLRP3和IL-6水平明显高于MS患者。复发期NMOSD患者EDSS评分与CSF NLRP3、mtDNA呈正相关。结论脑脊液中NLRP3炎性小体的水平可作为区分NMOSD和ms的诊断性生物标志物，在线粒体损伤后NLRP3炎性小体介导的焦亡可能在这些神经炎性疾病，尤其是NMOSD的发病机制中起重要作用。
BackgroundNeuromyelitis optica spectrum disorder (NMOSD) and MS are the most common autoimmune inflammatory demyelinating diseases of the CNS. However, the mechanisms of pathogenesis are still unclear. nucleotide-binding leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3), an important protein of the innate immune system that is activated by mitochondrial DNA (mtDNA), has been reported to be associated with various autoimmune disorders.ObjectiveTo assess the levels of cerebrospinal fluid (CSF) NLRP3, mtDNA and inflammation-associated cytokines (IL-1β, IL-6 and IL-17) in patients with NMOSD and MS, and to examine the correlations between these factors.Methods28 NMOSD patients, 15 MS patients, and 16 controls with non-inflammatory neurological diseases were recruited. NLRP3 inflammasome, IL-1β, IL-6 and IL-17 were measured by ELISA. CSF extracellular mtDNA was measured by qPCR. The severity of clinical presentation was evaluated by EDSS score.ResultsCSF levels of NLRP3, mtDNA, IL-1β, IL-6 and IL-17 were higher in NMOSD patients than in controls. Elevated CSF NLRP3, mtDNA and IL-6 were found in MS patients compared with controls. CSF NLRP3 and IL-6 levels were significantly higher in NMOSD patients than in MS patients. The EDSS scores of NMOSD patients during relapse were positively correlated with CSF NLRP3 and mtDNA.ConclusionOur findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.