【摘要】目的研究C3 肾小球病(C3 glomerulopathy,C3G)的临床病理特点及病因。方法回顾性分析1998～2015 年在北京大学第一医院诊断为C3G 患者的资料。应用酶联免疫吸附法检测Bb、C3a、C5a和sC5b-9 的水平及自身抗体的情况。应用外显子定制捕获测序的方法检测基因CFH、CFB、C3、CFI 和MCP的突变情况。结果本研究共纳入35 例C3G 患者，男女比例为27：8，平均年龄35 岁。患者临床表现和肾脏病理类型多样。患者血浆及尿液中的Bb、C3a、C5a 和sC5b-9 的水平均显著高于健康对照组(血浆：Z=- 6.900,Z=- 4.881,Z=- 5.322,Z=- 3.963； 尿液：Z=- 5.375,Z=- 5.527,Z=- 5.530,Z=- 5.651; 均P＜0.001)。18 例(51.4%)患者存在基因突变和(或)自身抗体。在平均随访的26.5 个月中，5 例患者发生终点事件。Cox 回归分析显示入院时血肌酐的水平是C3G 发生终点事件的独立危险因素(HR :1.010,95% CI: 1.001～1.019,P=0.034)。结论本研究提示C3G 主要病因包括补体基因突变和自身抗体。诊断时血肌酐的水平是C3G预后的独立危险因素。

【Abstract】Objective To study the clinico- pathological features and the etiology of patients with C3 glomerulopathy (C3G) in our cohort. Methods The clinico- pathological data of patients with C3G diagnosed in Peking University First Hospital from 1998 to 2015 were retrospectively analyzed. Concentrations of Bb, C3a, C5a, sC5b-9 and the presence of autoantibodies were detected by enzyme-linked immunosorbent assay. Mutations in complement-related genes CFH, CFB, C3, CFI and MCP were screened by using a target enrichment strategy for next-generation sequencing. Results Thirty-five patients with C3G were involved in this study. There were 27 males and 8 females with an average age of 35 years old. Their clinical symptoms and renal pathological types were variable. Concentrations of Bb, C3a, C5a and sC5b-9 in plasma and urine were significantly higher than healthy controls (in plasma: Z=-6.900, -4.881, -5.322 and -3.963, respectively; in urine: Z=-5.375, -5.527, -5.530 and -5.651, respectively; all P values ＜0.001). Etiologic analyses found that 18 patients (51.4% ) had genetic abnormalities and/or autoantibodies. During a median time of 26.5 months, 5 patients reached endpoints. Multivariate Cox proportional-hazard analysis revealed that serum creatinine level at onset was identified as the independent risk factor for the endpoints (HR: 1.010, 95% CI: 1.001～1.019, P=0.034). Conclusions Our study showed that dysregulation of the complement alternative pathway due to inherited and/or acquired defects was associated with C3G. Serum creatinine level at onset was an independent risk factor for prognosis in patients with C3G.