IRCCS, Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy.
IRCCS, Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Semin Nephrol. 2017 Sep;37(5):447-463. doi: 10.1016/j.semnephrol.2017.05.018.
The spectrum of immune-mediated glomerular diseases is wide, ranging from rare diseases with well-recognized genetic origins to more common and multifactorial diseases. Immune-mediated glomerular injury is complex and involves both the innate and the adaptive immune systems. In the past 20 years a huge effort has been undertaken to unravel the genetic basis of immune-mediated glomerular diseases. The discovery of abnormalities in genes encoding proteins of the alternative pathway of complement in more than 50% of patients with atypical hemolytic uremic syndrome (aHUS), and in approximately 20% of patients with membranoproliferative glomerulonephritis (MPGN), has highlighted the role of this complement pathway in the pathogenesis of immune-mediated glomerular diseases. aHUS-associated complement gene abnormalities mainly result in complement dysregulation restricted to the cell surface, whereas complement activation in the fluid phase prevails in most, but not all, genetic cases of MPGN. Results achieved in aHUS and MPGN have boosted interest in the impact of complement gene abnormalities and variations in the predisposition to more common, multifactorial kidney diseases, including IgA nephropathy and lupus nephritis. Emerging findings in these complex diseases have broadened our understanding of the fragile balance between the protective and harmful functions of the complement system.
免疫介导性肾小球疾病的范围很广，从具有明确遗传起源的罕见疾病到更为常见和多因素的疾病均有涉及。免疫介导性肾小球损伤复杂，涉及固有免疫和适应性免疫系统。在过去的 20 年中，人们做出了巨大的努力来揭示免疫介导性肾小球疾病的遗传基础。在超过 50%的非典型溶血尿毒综合征（aHUS）患者和约 20%的膜增生性肾小球肾炎（MPGN）患者中，发现了补体替代途径蛋白编码基因异常，这突显了该补体途径在免疫介导性肾小球疾病发病机制中的作用。aHUS 相关补体基因异常主要导致局限于细胞表面的补体失调，而在大多数但并非所有遗传性 MPGN 病例中，均以体液相中补体激活为主。在 aHUS 和 MPGN 中取得的成果，推动了人们对补体基因异常和易感性在更为常见的多因素肾脏疾病（包括 IgA 肾病和狼疮性肾炎）中作用的关注。在这些复杂疾病中出现的新发现，拓宽了我们对补体系统保护和有害功能之间脆弱平衡的理解。
