Giriş Murat, Bireller Sinem, Küçükali Cem İsmail, Hanağasi Haşmet, Değirmencioğlu Sevgin, Tüzün Erdem
Department of Neuroscience, Aziz Sancar Institute of Experimental Medical Research, İstanbul University, İstanbul, Turkey.
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medical Research, İstanbul University, İstanbul, Turkey.
Noro Psikiyatr Ars. 2017 Mar;54(1):67-71. doi: 10.5152/npa.2016.19421. Epub 2016 Dec 8.
Parenchymal neuro-Behçet disease (NBD) is encountered in 5%-15% of Behçet disease (BD) patients and is characterized by inflammation of the brainstem and diencephalon structures. Neuronal apoptosis has been shown to participate in neuronal cell loss. Anti-neuronal antibodies have been identified in NBD patients. However, the pathogenic properties of these antibodies have not been studied.
To delineate the potential pathogenic activity of serum antibodies on neurons, pooled sera from seven NBD patients and seven healthy controls were divided into purified immunoglobulin G (IgG) and IgG-depleted serum fractions, and each fraction was administered to cultured SH-SY5Y neuroblastoma cells. Cell death was evaluated with a toxicity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Moreover, expression levels of several apoptosis markers were evaluated with real time polymerase chain reaction (PCR).
Administration of NBD IgG to cultured SH-SY5Y cells induced significantly increased cell death and apoptosis compared with other treatments. NBD IgG also enhanced the mRNA expression levels of major apoptosis and cell survival pathway factors.
Our results suggest that IgGs isolated from the sera of NBD patients have a neurotoxic activity that is presumably mediated by apoptotic mechanisms.
实质型神经白塞病（NBD）见于5% - 15%的白塞病（BD）患者，其特征为脑干和间脑结构的炎症。已表明神经元凋亡参与神经元细胞丢失。在NBD患者中已鉴定出抗神经元抗体。然而，这些抗体的致病特性尚未得到研究。
为了描述血清抗体对神经元的潜在致病活性，将7例NBD患者和7例健康对照的混合血清分为纯化的免疫球蛋白G（IgG）和去除IgG的血清组分，并将每个组分施用于培养的SH - SY5Y神经母细胞瘤细胞。通过毒性测定和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色评估细胞死亡。此外，用实时聚合酶链反应（PCR）评估几种凋亡标志物的表达水平。
与其他处理相比，将NBD IgG施用于培养的SH - SY5Y细胞可显著增加细胞死亡和凋亡。NBD IgG还提高了主要凋亡和细胞存活途径因子的mRNA表达水平。
我们的结果表明，从NBD患者血清中分离出的IgG具有神经毒性活性，可能由凋亡机制介导。
