Molecular Otolaryngology and Renal Research Laboratories and the Departments of Internal Medicine and Pediatrics (Divisions of Nephrology), Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Department of Nephrology, Columbia University, New York, NY, USA.
Nat Rev Nephrol. 2019 Mar;15(3):129-143. doi: 10.1038/s41581-018-0107-2.
The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy - dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) - have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients - namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.
C3 肾小球疾病是一组罕见的肾脏疾病，其特征是补体失调发生在液相间和肾小球微环境中，导致肾脏活检样本中明显的补体 C3 沉积。C3 肾小球疾病的两个主要亚组——致密沉积物病（DDD）和 C3 肾小球肾炎（C3GN）——具有重叠的临床和病理特征，提示存在疾病连续统。补体替代途径的失调是 C3 肾小球疾病表现的基础，尽管末端途径的失调也很常见。在大多数患者中，疾病是由获得性因素驱动的——即针对 C3 或 C5 转化酶的自身抗体。这些自身抗体通过增加这些重要但正常寿命短的酶的半衰期来驱动补体失调。补体相关基因的遗传变异是一个不太常见的原因。目前尚无特异性治疗方法，尽管免疫抑制剂和末端补体途径抑制剂对一些患者有帮助。不幸的是，没有一种治疗方法普遍有效或能治愈疾病。总的来说，关于肾移植的有限数据表明，移植物受者的疾病复发（DDD 和 C3GN 均有）风险很高。正在进行临床试验以测试几种靶向替代补体途径的第一代药物的疗效。
