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前沿进展 | 神经白塞病患者的IgG可能通过凋亡机制而产生神经毒性

 渐近故乡时 2017-08-04

作者:Giriş Met al

译者:北医三院姚中强(yaozhongqiang@sina.com)  校正:孙琳

发布:柴静   审核:赵金霞

摘要:

引言:脑实质神经白塞病 (NBD) 见于5%-15% 白塞病 (BD) 患者,其特征是脑干和间脑结构的炎症。已经证实神经细胞凋亡参与了神经细胞丧失的过程。神经白塞患者血中检测出了抗神经元抗体。然而,这些抗体的致病性尚未研究过。

方法:为阐明血清抗体对神经元的潜在致病性,我们收集了7名神经白塞患者和7名健康对照的血清,并分为纯免疫球蛋白G (IgG) 和去除IgG的血清组分,而且,每一个组分都用来培养神经母细胞瘤细胞系SH-SY5Y。用毒性试验和末端转移酶介导的末端标记术(TUNEL)来评估细胞死亡。而且,使用实时定量PCR方法来评估数种凋亡相关标记物的表达。

结果:与其他处理相比,加入神经白塞患者IgG的培养的SH-SY5Y细胞死亡和凋亡均显著增加。 神经白塞患者的IgG也增加了细胞凋亡和存活通路主要分子的mRNA表达水平。

结论:我们的结果提示,来自神经白塞病患者的IgG可能通过凋亡机制而产生神经毒性。


附原文:Abstract  INTRODUCTION: Parenchymal neuro-Behçet disease (NBD) isencountered in 5%-15% of Behçetdisease (BD) patients and is characterizedby inflammation of the brainstem and diencephalon structures. Neuronalapoptosis has been shown to participate in neuronal cell loss. Anti-neuronalantibodies have been identified in NBD patients. However, the pathogenicproperties of these antibodies have not been studied.METHODS:To delineate the potentialpathogenic activity of serum antibodies on neurons, pooled sera from seven NBDpatients and seven healthy controls were divided into purified immunoglobulin G(IgG) and IgG-depleted serum fractions, and each fraction was administered tocultured SH-SY5Y neuroblastoma cells. Cell death was evaluated with a toxicityassay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)staining. Moreover, expression levels of several apoptosis markers wereevaluated with real time polymerase chain reaction (PCR).RESULTS:Administrationof NBD IgG to cultured SH-SY5Y cells induced significantly increased cell deathand apoptosis compared with other treatments. NBD IgG also enhanced the mRNAexpression levels of major apoptosis and cell survival pathway factors.CONCLUSION:Ourresults suggest that IgGs isolated from the sera of NBD patients have aneurotoxic activity that is presumably mediated by apoptotic mechanisms.

引自:Giriş MBireller SKüçükali CİHanağasi HDeğirmencioğluSTüzün E.Impact ofNeuro-Behçet Disease Immunoglobulin G on Neuronal Apoptosis. Noro Psikiyatr Ars. 2017 Mar;54(1):67-71.doi: 10.5152/npa.2016.19421. Epub 2016 Dec 8.








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