Membranous Nephropathy: A Journey From Bench to Bedside.
Membranous Nephropathy: A Journey From Bench to Bedside.
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DOI：
10.1053/j.ajkd.2016.01.030
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Salant DJ
中科院分区：
文献类型：
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作者：
Francis JM;Beck LH Jr;Salant DJ
来自一种与人类膜性肾病（MN）高度相似的动物模型的经验，增进了我们对这种器官特异性自身免疫疾病的发病机制以及肾病综合征常见病因的理解。一旦确定循环抗体与固有足细胞抗原结合时，实验性MN所特有的上皮下免疫沉积物是原位形成的，那么人类抗原的确定就只是时间问题。M型磷脂酶A2受体1（PLA2R）是原发性MN的主要靶抗原，而含血小板反应蛋白1型结构域7A（THSD7A）是近期发现的一种次要抗原。抗PLA2R的血清学检测以及肾活检标本的PLA2R染色在大多数人群中对原发性MN的诊断具有超过90%的特异性和70% - 80%的敏感性。这些检测可将大多数原发性MN病例与其他系统性疾病相关的MN区分开来，并且抗PLA2R的连续滴度有助于监测治疗反应。移植前抗PLA2R检测呈阳性也有助于预测移植后复发的风险。PLA2R内靶表位的确定以及原发性MN与II类主要组织相容性和PLA2R1变异的遗传关联是我们对这种疾病不断深入理解的另外两个例子。
Lessons from an animal model that faithfully resembles human membranous nephropathy (MN) have informed our understanding of the pathogenesis of this organ-specific autoimmune disease and common cause of the nephrotic syndrome. Once it was established that the subepithelial immune deposits that characterize experimental MN form in situ when circulating antibodies bind to an intrinsic podocyte antigen, it was merely a matter of time before the human antigen was identified. The M-type phospholipase A2 receptor 1 (PLA2R) represents the major target antigen in primary MN, and thrombospondin type 1 domain-containing 7A (THSD7A) was more recently identified as a minor antigen. Serological tests for anti-PLA2R as well as kidney biopsy specimen staining for PLA2R exhibit more than 90% specificity and 70% to 80% sensitivity for the diagnosis of primary MN in most populations. The assays distinguish most cases of primary MN from MN associated with other systemic diseases, and sequential titers of anti-PLA2R are useful to monitor treatment response. A positive pre-transplantation test for anti-PLA2R is also helpful for predicting the risk of post-transplantation recurrence. Identification of target epitopes within PLA2R as well as the genetic association of primary MN with class II major histocompatibility and PLA2R1 variants are 2 additional examples of our evolving understanding of this disease.