C3肾小球病的临床病理特征及病因分析

A retrospective analysis of clinico-pathological features and etiology in C3 glomerulopathy: a single center study

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。

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.