Antibodies in patients with neuropsychiatric systemic lupus erythematosus

Antibodies in patients with neuropsychiatric systemic lupus erythematosus
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DOI:
10.1212/wnl.0b013e3181dad590
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发表时间:
2010-04-27
期刊:
影响因子:
9.9
通讯作者:
Inuzuka, T.
Inuzuka, T.
中科院分区:
医学1区
文献类型:
--
作者:
Kimura, A.;Kanoh, Y.;Inuzuka, T.

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目的:目的:探讨自身抗体在神经精神系统性红斑狼疮(NPSLE)患者中的作用靶点。背景:NPSLE的发病机制可能与自身抗体介导的神经功能障碍、血管病变和凝血功能障碍有关。然而,很少有自身抗体对NPSLE敏感和特异,因为与SLE相关的神经精神综合征在病因和表现上是多样的。我们通过双向电泳、蛋白质印迹和液相色谱-串联质谱鉴定了7例NPSLE患者和12例健康对照血清中的抗脑抗原抗体结果:在NPSLE患者血清中检测到6种抗体。这6种抗体中的一种在患有精神病的NPSLE患者中针对Rab鸟苷二磷酸解离抑制剂α(α GDI)(其在神经元中特别丰富并调节突触囊泡胞吐)的抗体中发现。我们通过人重组α-GDI的一维免疫印迹测试了更多的样品。NPSLE伴精神病患者的抗α-GDI抗体阳性率显著高于(80%,4/5)比无精神病的NPSLE患者(0%,0/13),无神经精神症状的系统性红斑狼疮患者(5.3%,1/19),多发性硬化症患者(0%,0/12),感染性脑膜脑炎患者(0%,0/13),多发性神经病患者(0%,0/10),精神病综合征患者(0%,0/10)和健康对照组(0%,0/12).结论:我们建议反-Rab鸟苷二磷酸解离抑制剂α抗体作为神经精神相关性精神病的诊断标志物值得进一步探索系统性红斑狼疮神经病学(R)2010; 74:1372-1379
Objective: To investigate a target for antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).Background: Pathogenesis of NPSLE may be related to autoantibody-mediated neural dysfunction, vasculopathy, and coagulopathy. However, very few autoantibodies are sensitive and specific to NPSLE because the neuropsychiatric syndromes associated with SLE are diverse in cause and presentation.Methods: We identified antibodies against brain antigens in the sera of 7 patients with NPSLE and 12 healthy controls by 2-dimensional electrophoresis, followed by Western blotting and liquid chromatography-tandem mass spectrometry (LC-MS/MS), using rat brain proteins as the antigen source.Results: Six antibodies were detected in patients with NPSLE. One of these 6 antibodies was found in antibodies against Rab guanosine diphosphate dissociation inhibitor alpha (alpha GDI) (which is specifically abundant in neurons and regulates synaptic vesicle exocytosis) in patients with NPSLE with psychosis. We tested more samples by 1-dimensional immunoblotting of human recombinant alpha GDI. Positivity of the anti-alpha GDI antibody was significantly higher in patients with NPSLE with psychosis (80%, 4 of 5) than in patients with NPSLE without psychosis (0%, 0 of 13), patients with systemic lupus erythematosus without neuropsychiatric symptoms (5.3%, 1 of 19), patients with multiple sclerosis (0%, 0 of 12), patients with infectious meningoencephalitis (0%, 0 of 13), patients with polyneuropathy (0%, 0 of 10), patients with psychotic syndromes (0%, 0 of 10), and healthy controls (0%, 0 of 12).Conclusions: We propose that the anti-Rab guanosine diphosphate dissociation inhibitor alpha antibody is a candidate for further exploration as diagnostic marker of psychosis associated with neuropsychiatric systemic lupus erythematosus. Neurology (R) 2010; 74: 1372-1379