PDF(Pubmed)
Abstract：
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent years have witnessed significant improvements in the understanding of the pathogenesis of IgAN and particularly, the pathogenic role of complement activation. The alternative complement pathway is the major complement cascade activator in IgAN, and glomerular C3 deposition has been shown to correlate with disease progression. In addition, several studies have provided insight into the pathogenic role of factor H-related proteins -1 and -5 in IgAN, as independent players in complement dysregulation. The lectin pathway has also been shown to be associated with the severity of IgAN. Glomerular deposition of C4d has been associated with increased histologic disease activity, faster decline in estimated glomerular filtration rate and higher risk of kidney failure. On the other hand, although overlooked in the Oxford classification, numerous studies have shown that the coexistence of thrombotic microangiopathy in IgAN is a significant indicator of a poorer prognosis. All the breakthroughs in the understanding of the contributing role of complement in IgAN have paved the way for the development of new complement-targeted therapies in this disease. Several ongoing trials are evaluating the efficacy of new agents against factor B (iptacopan, Ionis-FB-LRX), C3 (pegcetacoplan), factor D (vemircopan, pelecopan), C5 (ravulizumab, cemdisiran) and C5a receptor 1 (avacopan). In this study, we provide a comprehensive review of the role of complement in IgAN, including the emerging mechanisms of complement activation and the promising potential of complement inhibitors as a viable treatment option for IgAN.
摘要：
免疫球蛋白A肾病(IgAN)是全球最常见的原发性肾小球肾炎。近年来,人们对IgAN发病机制的认识有了显著的提高,补体激活的致病作用。补体旁路途径是IgAN中主要的补体级联激活剂，肾小球C3沉积已被证明与疾病进展相关。此外,几项研究提供了对H因子相关蛋白-1和-5在IgAN中的致病作用的见解，作为互补失调的独立参与者。凝集素途径也已显示与IgAN的严重程度相关。C4d的肾小球沉积与组织学疾病活动增加有关，估计肾小球滤过率下降更快，肾衰竭风险更高。另一方面,尽管在牛津分类中被忽视了，许多研究表明，IgAN中血栓性微血管病变的共存是预后较差的重要指标。对补体在IgAN中的作用的理解的所有突破为在这种疾病中开发新的补体靶向疗法铺平了道路。一些正在进行的试验正在评估新药对因子B的疗效(伊塔科潘，Ionis-FB-LRX)，C3(pegcetacoplan),因子D(vemircopan，pelecopan),C5（ravulizumab，cemdisiran）和C5a受体1（avacopan）。在这项研究中,我们对补体在IgAN中的作用进行了全面综述，包括新出现的补体激活机制以及补体抑制剂作为IgAN可行治疗选择的潜在潜力.
