Bucillamine induces membranous glomerulonephritis
Bucillamine induces membranous glomerulonephritis
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DOI：
10.1053/ajkd.2002.31987
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发表时间：
2002-04-01
影响因子：
13.2
通讯作者：
Yamada, A
中科院分区：
文献类型：
--
作者：
Nagahama, K;Matsushita, H;Yamada, A
类风湿性关节炎（RA）与多种肾脏组织病理学病变有关，如淀粉样变性、系膜增生性肾小球肾炎和膜性肾小球肾炎（MGN）。布西拉明（BCL）是一种缓解疾病的抗风湿药物，其化学结构和副作用与D-青霉胺相似，可诱导RA的MGN。有一些MGN发生与BCL治疗相关的报告。然而，由于缺乏对肾小球病变中免疫球蛋白沉积的详细分析，这些研究没有阐明BCL诱导的MGN的发病机制。我们评估了来自6例RA患者的7份活检标本，这些患者在出现蛋白尿之前接受了平均72.5 g BCL剂量的BCL治疗。光镜检查显示轻度至中度系膜增生。两个活检标本显示沿沿着肾小球毛细血管壁的棘突。在所有病例中均观察到免疫球蛋白G（IgG）沿着肾小球毛细血管壁的颗粒状沉积，5份标本除IgG 4外还显示IgG 2和/或IgG 3组分的沉积。此外，在电镜下，上皮下致密沉积物分布在四个活检标本节段性。IgG 4在原发性MGN中呈弥漫性分布，是沉积的主要IgG亚类。因此，BCL诱导的和特发性MGN在肾小球内沉积的IgG亚类和沉积模式方面存在明显差异。由于IgG 3对C1 q具有最强的亲和力，因此这些发现表明BCL诱导的MGN比特发性MGN更有效地激活经典途径，并且这两种疾病的发病机制不同。(C)2002年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
A variety of renal histopathologic lesions, such as amyloidosis, mesangial proliferative glomerulonephritis, and membranous glomerulonephritis (MGN), are associated with rheumatoid arthritis (RA). Bucillamine (BCL), a disease-modifying antirheumatic drug, has a chemical structure and side-effect profile similar to that of D-penicillamine, which can induce MGN in RA. There are a few reports of MGN occurring in association with BCL treatment. However, lacking detailed analyses of immunoglobulin deposition In glomerular lesions, these studies did not elucidate the pathogenesis of BCL-induced MGN. We evaluated seven biopsy specimens from six patients with RA who had undergone BCL treatment with a mean BCL dose of 72.5 g before the appearance of proteinuria. Light microscopic evaluation showed mild to moderate mesangial proliferation. Two biopsy specimens showed spikes along glomerular capillary walls. Granular deposition of Immunoglobulin G (IgG) along glomerular capillary walls was seen in all cases, and five specimens showed deposition of IgG2 and/or IgG3 components, in addition to IgG4. Furthermore, subepithelial dense deposits were distributed segmentally in four biopsy specimens on electron microscopy. IgG4, reported to be the predominant IgG subclass deposited, Is distributed diffusely in idiopathic MGN. Thus, there were obvious differences between BCL-induced and idiopathic MGN in regard to both IgG subclasses deposited and deposition pattern within the glomerulus. Because IgG3 has the strongest affinity for C1q, these findings suggest that BCL-induced MGN activates the classical pathway more efficiently than Idiopathic MGN and that the pathogenesis is different between these two diseases. (C) 2002 by the National Kidney Foundation, Inc.