Matsueda Yu, Arinuma Yoshiyuki, Nagai Tatsuo, Hirohata Shunsei
Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Sagamihara, Japan.
Lupus Sci Med. 2018 Oct 10;5(1):e000281. doi: 10.1136/lupus-2018-000281. eCollection 2018.
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).
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)×10).
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.
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.
近期研究表明，针对内皮细胞上葡萄糖调节蛋白78（GRP78）的自身抗体可促进血脑屏障（BBB）损伤。本研究检测血清抗GRP78抗体是否可能参与神经精神性狼疮（NPSLE）的发病机制。
采集了129例系统性红斑狼疮（SLE）患者的血清样本（58例患有NPSLE弥漫性精神/神经心理综合征（弥漫性NPSLE），30例患有神经综合征（局灶性NPSLE），21例患有狼疮性肾炎（LN），20例无NPSLE或LN（仅SLE）），35例非SLE风湿性疾病（非SLE RD）患者的血清样本以及24例健康对照（HC）的血清样本。以重组GRP78作为抗原，采用酶联免疫吸附测定（ELISA）法检测抗GRP78水平。还采集了88例NPSLE患者的脑脊液（CSF）样本。通过Q白蛋白（（脑脊液白蛋白/血清白蛋白）×10）评估血脑屏障功能。
与非SLE RD或HC相比，SLE患者血清抗GRP78水平显著升高。NPSLE、LN和仅SLE患者的血清抗GRP78水平无显著差异。值得注意的是，急性意识模糊状态（ACS）患者的血清抗GRP78水平显著高于非ACS弥漫性NPSLE患者（p = 0.0001）或局灶性NPSLE患者（p = 0.0002）。最后，在NPSLE患者中，血清抗GRP78水平与Q白蛋白显著相关（r = 0.294，p = 0.0054）。
这些结果表明，抗GRP78抗体与弥漫性NPSLE的发生有关，尤其是ACS。因此，数据表明抗GRP78抗体可能通过血脑屏障损伤促成ACS的发生。
