M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.
M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.
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DOI：
10.1056/nejmoa0810457
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发表时间：
2009-07-02
期刊：
影响因子：
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通讯作者：
Salant DJ
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作者：
Beck LH Jr;Bonegio RG;Lambeau G;Beck DM;Powell DW;Cummins TD;Klein JB;Salant DJ
特发性膜性肾病是一种抗体介导的自身免疫性肾小球疾病，是肾病综合征的一种常见形式。血清学诊断一直难以捉摸，因为靶抗原是未知的。我们进行了蛋白质印迹法的蛋白质提取物从正常人肾小球与血清样品从患者的特发性或继发性膜性肾病或其他蛋白尿或自身免疫性疾病和正常对照。我们使用质谱分析反应蛋白条带，并用单特异性抗体确认靶抗原的身份和位置。来自37例特发性但非继发性膜性肾病患者中的26例（70%）的血清样本在非还原性肾小球提取物中特异性鉴定了185 kD糖蛋白。反应蛋白条带的质谱检测到M型磷脂酶A2受体（PLA2R）。反应性血清标本识别重组PLA2R，并结合相同的185 kD肾小球蛋白的单特异性抗PLA2R抗体。膜性肾病患者血清中的抗PLA2R自身抗体主要为IgG 4，这是肾小球沉积物中的主要免疫球蛋白亚类。PLA 2R在正常人肾小球足细胞中表达，并与膜性肾病患者肾小球免疫沉积物中的IgG 4共定位。IgG洗脱从这样的存款在特发性膜性肾病患者，但不是在狼疮膜性或伊加肾病，承认PLA2R。大多数患有特发性膜性肾病的患者具有针对PLA2R中的构象依赖性表位的抗体。PLA2R存在于正常足细胞和特发性膜性肾病患者的免疫沉积物中，表明PLA2R是这种疾病的主要抗原。
Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown. We performed Western blotting of protein extracts from normal human glomeruli with serum samples from patients with idiopathic or secondary membranous nephropathy or other proteinuric or autoimmune diseases and from normal controls. We used mass spectrometry to analyze the reactive protein bands and confirmed the identity and location of the target antigen with a monospecific antibody. Serum samples from 26 of 37 patients (70%) with idiopathic but not secondary membranous nephropathy specifically identified a 185-kD glycoprotein in non-reduced glomerular extract. Mass spectrometry of the reactive protein band detected the M-type phospholipase A2 receptor (PLA2R). Reactive serum specimens recognized recombinant PLA2R and bound the same 185-kD glomerular protein as did the monospecific anti-PLA2R antibody. Anti-PLA2R autoantibodies in serum samples from patients with membranous nephropathy were mainly IgG4, the predominant immunoglobulin subclass in glomerular deposits. PLA2R was expressed in podocytes in normal human glomeruli and colocalized with IgG4 in immune deposits in glomeruli of patients with membranous nephropathy. IgG eluted from such deposits in patients with idiopathic membranous nephropathy, but not in those with lupus membranous or IgA nephropathy, recognized PLA2R. A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA2R. PLA2R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA2R is a major antigen in this disease.