Antigen Identification in Membranous Nephropathy Moves toward Targeted Monitoring and New Therapy
Antigen Identification in Membranous Nephropathy Moves toward Targeted Monitoring and New Therapy
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DOI：
10.1681/asn.2009121220
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发表时间：
2010-04-01
影响因子：
13.6
通讯作者：
Debiec, Hanna
中科院分区：
文献类型：
--
作者：
Ronco, Pierre;Debiec, Hanna
膜性肾病是一种以肾小球基底膜外侧免疫沉积物积累为特征的疾病，是白种人成人特发性肾病综合征的最常见原因。在Heymann于1959年描述的大鼠模型中，抗体的靶抗原是巨蛋白，一种在大鼠肾小球中表达但在人肾小球中不存在的多配体受体。在过去几年中，在人膜性肾病中已鉴定出两种主要抗原。第一个是中性肽链内切酶，它是与膜性肾病新生儿病例相关的同种抗原，这种病发生在中性肽链内切酶缺陷母亲的新生儿中。第二种是 M 型磷脂酶 A2 受体 (PLA(2)R)，这是在成人特发性膜性肾病中发现的第一个自身抗原。巨蛋白、中性肽链内切酶和 PLA(2)R 均在足细胞表面表达，作为循环抗体的靶标，从而导致原位免疫复合物形成、补体激活和蛋白尿。最近发现的中性内肽酶和 PLA(2)R 为监测人类疾病活动提供了新工具，并且对于设计新的抗原驱动的治疗策略具有价值。
Membranous nephropathy, a disease characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane, is the most common cause of idiopathic nephrotic syndrome in Caucasian adults. In the rat model described by Heymann in 1959, the target antigen of antibodies is megalin, a multiligand receptor expressed in the rat glomerulus but absent from the human glomerulus. In the past few years, two major antigens have been identified in human membranous nephropathy. The first is neutral endopeptidase, the alloantigen involved in neonatal cases of membranous nephropathy that occur in new-borns from neutral endopeptidase-deficient mothers. The second is the type-M phospholipase A2 receptor (PLA(2)R), the first autoantigen identified in idiopathic membranous nephropathy in the adult. Megalin, neutral endopeptidase, and PLA(2)R are all expressed on the podocyte surface where they serve as targets for circulating antibodies, which lead to in situ immune complex formation, complement activation, and proteinuria. The recent discovery of neutral endopeptidase and PLA(2)R provides new tools for monitoring human disease activity and should be of value in designing new antigen-driven therapeutic strategies.