Elevation of serum anti–glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus
Elevation of serum anti–glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus
复制标题
神经精神系统性红斑狼疮血清抗葡萄糖调节蛋白78抗体升高
DOI：
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发表时间：
2018
影响因子：
3.9
通讯作者：
S. Hirohata
中科院分区：
文献类型：
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作者：
Y. Matsueda;Y. Arinuma;T. Nagai;S. Hirohata
目的近年来的研究表明，内皮细胞上针对葡萄糖调节蛋白78（GRP 78）的自身抗体可促进血脑屏障（BBB）的损伤。本研究探讨血清抗GRP 78抗体是否可能参与神经精神系统性红斑狼疮（NPSLE）的发病机制。方法收集129例SLE患者（弥漫性NPSLE患者58例，局灶性NPSLE患者30例，狼疮性肾炎（LN）患者21例，单纯SLE患者20例）、35例非SLE风湿性疾病患者（non-SLE RD）和24例健康对照者（HC）的血清标本。使用重组GRP 78作为抗原，用ELISA测量抗GRP 78水平。还从88例NPSLE患者中获得脑脊液（CSF）样本。采用Q白蛋白（CSF白蛋白/血清白蛋白）×103评价血脑屏障功能。结果SLE患者血清抗GRP 78抗体水平显著高于非SLE RD或HC患者。血清抗GRP 78水平在NPSLE、LN和SLE之间无显著差异。值得注意的是，急性意识模糊状态（ACS）中的血清抗GRP 78水平显著高于非ACS弥漫性NPSLE（p=0.0001）或局灶性NPSLE（p=0.0002）。最后，血清抗GRP 78水平与Q白蛋白在NPSLE中显著相关（r=0.294，p=0.0054）。结论抗GRP 78抗体与弥漫性NPSLE尤其是ACS的发生有关。因此，这些数据表明，抗GRP 78抗体可能通过BBB的损伤而促进ACS的发展。
Objective Recent studies have demonstrated that autoantibodies directed against glucose-regulated protein 78 (GRP78) on endothelial cells promote blood–brain barrier (BBB) damages. The present study examined whether serum anti-GRP78 antibodies might be involved in the pathogenesis of neuropsychiatric SLE (NPSLE). Methods Serum samples were obtained from 129 patients with SLE (58 patients with diffuse psychiatric/neuropsychological syndromes of NPSLE (diffuse NPSLE), 30 with neurological syndromes (focal NPSLE), 21 with lupus nephritis (LN), 20 without NPSLE or LN (SLE alone)), from 35 patients with non-SLE rheumatic diseases (non-SLE RD) and from 24 healthy controls (HC). Anti-GRP78 levels were measured with an ELISA, using recombinant GRP78 as antigens. Cerebrospinal fluid (CSF) samples were also obtained from 88 patients with NPSLE. The BBB function was evaluated by Q albumin ((CSF albumin/serum albumin)×103). Results Serum anti-GRP78 levels were significantly elevated in SLE compared with non-SLE RD or HC. There were no significant differences in serum anti-GRP78 levels among NPSLE, LN and SLE alone. Of note, serum anti-GRP78 levels were significantly higher in acute confusional state (ACS) than in non-ACS diffuse NPSLE (p=0.0001) or in focal NPSLE (p=0.0002). Finally, serum anti-GRP78 levels were significantly correlated with Q albumin (r=0.294, p=0.0054) in NPSLE. Conclusion These results indicate that anti-GRP78 antibodies are associated with the development of diffuse NPSLE, especially ACS. Thus, the data suggest that anti-GRP78 antibodies might contribute to the development of ACS through the damages of BBB.