Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus
Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus
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DOI：
10.1002/art.23399
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Hirohata, Shunsei
中科院分区：
文献类型：
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作者：
Arinuma, Yoshiyuki;Yanagida, Tamiko;Hirohata, Shunsei
目标。探讨脑脊液（CSF）中n -甲基- d -天冬氨酸受体亚基NR2抗体（抗NR2）与系统性红斑狼疮（NPSLE）神经精神症状的关系。从56例NPSLE患者（38例为弥漫性精神/神经心理综合征[弥漫性NPSLE]， 18例为神经综合征或周围神经病变[局灶性NPSLE]）和20例非炎症性神经疾病对照患者中获得配对血清和脑脊液标本。采用含有NR2细胞外配体结合域的合成肽，采用酶联免疫吸附法测定IgG抗NR2抗体。用流式细胞术检测亲和纯化的抗nr2与人神经母细胞瘤细胞株SK-N-MC的结合。纯化的抗nr2结合到SK-N-MC细胞表面。与对照组和局灶性NPSLE患者相比，弥漫性NPSLE患者脑脊液中抗nr2抗体水平显著升高，而3组间血清抗nr2水平无显著差异。38例弥漫性NPSLE患者中有31例（81.6%），18例局灶性NPSLE患者中有8例（44.4%），脑脊液抗nr2水平高于对照组平均水平3 SD以上（χ 2检验P = 0.0120）。这些结果表明，抗nr2是抗神经元抗体的一个组成部分，更重要的是，脑脊液中的抗nr2抗体与弥漫性NPSLE相关，而血清中没有。
Objective. To explore the association of antibodies directed against N-methyl-D-aspartate receptor subunit NR2 (anti-NR2) in cerebrospinal fluid (CSF) with neuropsychiatric manifestations in systemic lupus erythematosus (NPSLE).Methods. Paired serum and CSF specimens were obtained from 56 patients with NPSLE (38 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 18 with neurologic syndromes or peripheral neuropathy [focal NPSLE]) and from 20 control patients with noninflammatory neurologic diseases. IgG anti-NR2 antibodies were measured by enzyme-linked immunosorbent assay using synthetic peptide containing the extracellular ligand-binding domain of NR2. The binding of affinity-purified anti-NR2 to human neuroblastoma cell line SK-N-MC was examined by flow cytometry.Results. Purified anti-NR2 bound to the surface of SK-N-MC cells. Levels of anti-NR2 antibodies in CSF were significantly elevated in patients with diffuse NPSLE compared with levels in control patients or those with focal NPSLE, whereas there were no significant differences in serum anti-NR2 levels among the 3 groups. In 31 of the 38 patients with diffuse NPSLE (81.6%) and 8 of the 18 patients with focal NPSLE (44.4%), CSF anti-NR2 levels were more than 3 SD above the mean level in the control patients (P = 0.0120 by chi-square test).Conclusion. These results indicate that anti-NR2 is a constituent of antineuronal antibodies and, more importantly, that anti-NR2 antibodies in CSF, but not in serum, are associated with diffuse NPSLE.