Association of anti-NMDAR2 antibodies with the pathogenesis of neuropsychiatric systemic lupus erythematosus

抗 NMDAR2 抗体与神经精神系统性红斑狼疮发病机制的关系

• 批准号: 15591063
• 负责人: YOSHIO Taku
• 金额: $ 1.86万
• 依托单位: JICHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591063/
• 关键词: NMDA receptor snbunits NR2a and NR2b; anti-NMDA R2 antibodies; anti-dsDNA antibodies; systemic lupus erythematosus(SLE); neuropsychiatric SLE(NPSLE); antiribosomal P protein antibodies; endothelial cell activation; N-methyl-D-asparateレセプター; SLE

Firstly it was investigated whether IgG anti-NMDAR2 antibodies (anti-NR2) in the cerebrospinal fluid (CSF) and serum of patients with SLE are related to neuropsychiatric SLE (NPSLE). CSF and serum samples from 80 patients with SLE were used. They were divided into 4 groups (1^<st> group : neurologic syndromes of the central nervous system(CNS), 2^<nd> group : diffuse psychiatric/neuropsychological syndromes, 3^<rd> group : complex presentations (neurologic syndromes of the CNS+diffuse psychiatric/neuropsychological syndromes) and 4^<th> group : non-NPSLE). CSF and serum IgG anti-NR2 titers were measured by ELISA using synthetic DWEYSVWLSN peptide as the antigen. Serum IgG anti-NR2 were not significantly associated with the presence of NPSLE. CSF IgG anti-NR2 were significantly associated with the presence of NPSLE, especially complex presentations. CSF IgG anti-NR2 titers were significantly positive-correlated with each of serum CSF IgG anti-NR2 titers and CSF IgG anti-P titers in patients with NPSLE. These results suggest that the presence of IgG anti-NR2 in the CSF of patients with SLE may be associated with the appearance and development of NPSLE, especially complex presentations.Secondly purified IgG anti-NR2 of 14 patients with SLE were tested for their ability to 1)bind to ds DNA, 2)bind to EC, 3)modulate adhesion molecule expression on EC surface and cytokine production from EC. Purified IgG of 5 normal controls were used as negative controls. Purified anti-NR2 bound to dsDNA with IgG-dose-dependence. They bound to EC and stimulated the up-regulation of adhesion molecule expression and IL-6 and IL-8 production more significantly than IgG of normal controls. These results suggest the possibility that anti-NR2 as anti-dsDNA antibodies may bind to EC surface and activate EC in SLE. Such events on EC in the central nervous system may lead to the damage of blood-brain barrier, resulting in the appearance and development of NPSLE.

本研究首先探讨SLE患者脑脊液和血清中抗NMDAR 2抗体（抗NR 2抗体）IgG与神经精神性SLE（NPSLE）的关系。收集了80例SLE患者的CSF和血清标本。他们被分为4组（1^<st>组：中枢神经系统（CNS）的神经系统综合征，2^<nd>组：弥漫性精神/神经心理综合征，3^<rd>组：复杂表现（CNS神经系统综合征+弥漫性精神/神经心理综合征）和4^<th>组：非NPSLE）。使用合成的DWEYSVWLSN肽作为抗原，通过ELISA测量CSF和血清IgG抗NR 2滴度。血清IgG抗NR 2与NPSLE的存在无显著相关性。CSF IgG抗NR 2与NPSLE的存在显著相关，特别是复杂的介绍。NPSLE患者CSF IgG抗NR 2滴度与血清CSF IgG抗NR 2滴度和CSF IgG抗P滴度均呈显著正相关。结果表明，SLE患者脑脊液中IgG抗NR 2抗体的存在可能与NPSLE的发生、发展有关，尤其是与NPSLE的复杂表现有关。其次，检测了14例SLE患者脑脊液中IgG抗NR 2抗体与dsDNA结合，与EC结合，调节EC表面粘附分子表达和EC产生细胞因子的能力。5例正常人IgG纯化液作为阴性对照。纯化的抗NR 2以IgG剂量依赖性与dsDNA结合。与正常对照组IgG相比，它们与EC结合，刺激EC粘附分子表达和IL-6、IL-8产生的上调作用更明显。这些结果表明，抗NR 2的抗dsDNA抗体的可能性，结合EC表面和激活EC在SLE。中枢神经系统EC的这些事件可能导致血脑屏障的损伤，从而导致NPSLE的发生和发展。

项目成果

Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus.

• 发表时间: 2005
• 期刊: The Journal of rheumatology
• 作者: T. Yoshio;D. Hirata;K. Onda;H. Nara;S. Minota