Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies
Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies
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DOI：
10.1038/ki.2012.63
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发表时间：
2012-08-01
影响因子：
19.6
通讯作者：
Fremeaux-Bacchi, Veronique
中科院分区：
文献类型：
--
作者：
Servais, Aude;Noel, Laure-Helene;Fremeaux-Bacchi, Veronique
致密沉积性疾病和肾小球肾炎伴孤立的C3沉积是以C3沉积在肾小球基底膜内或沿肾小球基底膜沉积为特征的肾小球疾病。以前的研究发现补体替代途径的失调与这些疾病的发病机制之间存在联系。我们分析了134例患者中获得性和遗传性补体异常的作用，其中29例为致密沉积疾病，56例为肾小球肾炎伴孤立的C3沉积，49例为I型膜增生性肾小球肾炎，起病于成人和儿童。共有53例患者表现为低C3水平，65例C3肾病因子阳性，在致密沉积病患者中明显高于其他组织学类型。在24名患者中发现了CFH和CFI基因突变，其中一半患者与C3肾病因子相关。在26例I型膜增生性肾小球肾炎患者中发现补体替代途径异常的证据。补体因子H Y402H变异在致密沉积病中显著增加。因此，我们的研究结果表明，在C3肾小球疾病和免疫复合物介导的肾小球疾病的发病机制中，液相交替途径失调起着关键作用。C3矿床的本地化可能受到MCP表达的影响。肾脏国际(2012年)82454464；DOI：10.1038/ki.2012.63；在线发布
Dense deposit disease and glomerulonephritis with isolated C3 deposits are glomerulopathies characterized by deposits of C3 within or along the glomerular basement membrane. Previous studies found a link between dysregulation of the complement alternative pathway and the pathogenesis of these diseases. We analyzed the role of acquired and genetic complement abnormalities in a cohort of 134 patients, of whom 29 have dense deposit disease, 56 have glomerulonephritis with isolated C3 deposits, and 49 have primary membranoproliferative glomerulonephritis type I, with adult and pediatric onset. A total of 53 patients presented with a low C3 level, and 65 were positive for C3 nephritic factor that was significantly more frequently detected in patients with dense deposit disease than in other histological types. Mutations in CFH and CFI genes were identified in 24 patients associated with a C3 nephritic factor in half the cases. We found evidence for complement alternative pathway dysregulation in 26 patients with membranoproliferative glomerulonephritis type I. The complement factor H Y402H variant was significantly increased in dense deposit disease. We identified one at-risk membrane cofactor protein (MCP) haplotype for glomerulonephritis with isolated C3 deposits and membranoproliferative glomerulonephritis type I. Thus, our results suggest a critical role of fluid-phase alternative pathway dysregulation in the pathogenesis of C3 glomerulopathies as well as in immune complex-mediated glomerular diseases. The localization of the C3 deposits may be under the influence of MCP expression.Kidney International (2012) 82, 454-464; doi:10.1038/ki.2012.63; published online 28 March 2012