Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI

Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI
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DOI:
10.1177/0961203307085112
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发表时间:
2008-01-01
期刊:
影响因子:
2.6
通讯作者:
Inuzuka, T.
Inuzuka, T.
中科院分区:
医学4区
文献类型:
--
作者:
Kimura, A.;Sakurai, T.;Inuzuka, T.

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神经精神系统性红斑狼疮(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。我们遇到了一名NPSLE患者,其脑部在T2加权磁共振(MR)图像上显示大脑白色物质、小脑和中小脑脚存在特征性弥漫性对称高信号病变。在这项研究中,我们调查了所有的抗原,反应强烈的自身抗体在这个病人的血清中的双向电泳(2DE),然后通过蛋白质印迹(WB)和液相色谱-串联质谱(LC-MS/MS)使用大鼠脑蛋白作为抗原源。结果,我们确定了四个抗原,β-肌动蛋白,α-internexin,60 kDa热休克蛋白(Hsp 60)和胶质细胞酸性蛋白(GFAP)。有几个报告检测抗内皮细胞抗体(AECA)在SLE患者。最近,在SLE患者血清中与AECA反应的抗原之一已被鉴定为人Hsp 60。我们推测,我们的病人的脑MR图像上的异常发现可能是由于微循环障碍与血管内皮细胞损伤的抗体介导的热休克蛋白60。这种蛋白质组学分析是一个有用的工具,用于识别自身抗原的自身免疫性疾病涉及自身抗体。狼疮(2008)17,16-20。
The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) may be related to autoantibody-mediated neural dysfunction, vasculopathy and coagulopathy. We encountered an NPSLE patient whose brain showed characteristic diffuse symmetrical hyperintensity lesions in the cerebral white matter, cerebellum and middle cerebellar peduncles on T2-weighted magnetic resonance (MR) images. In this study, we investigated all the antigens that reacted strongly with autoantibodies in this patient's serum by two-dimensional electrophoresis (2DE), followed by western blotting (WB) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using rat brain proteins as the antigen source. As a result, we identified four antigens as beta-actin, alpha-internexin, 60 kDa heat-shock protein (Hsp60) and glial fibrillary acidic protein (GFAP). There are several reports on the detection of anti-endothelial cell antibodies (AECAs) in an SLE patients. Recently, one of the antigens reacting with AECAs in SLE patient's sera has been identified as human Hsp60. We speculated that the abnormal findings on brain MR images of our patient may be due to impairment of microcirculation associated with vascular endothelial cell injury mediated by the antibody against Hsp60. This proteomic analysis is a useful tool for identifying autoantigens in autoimmune diseases involving autoantibodies. Lupus (2008) 17, 16-20.