低C3血症及补体旁路途径异常活化与IgA肾病临床病理特征及预后分析

The correlation of decreased serum C3 and abnormal activation of alternative complement pathway with clinicopathological manifestations and prognosis of IgA nephropathy

目的:探讨低C3血症及补体旁路途径异常活化与Ig A肾病(Ig AN)临床、病理严重程度及预后的关系。方法:回顾性收集2010年1月至2014年12月上海交通大学医学院附属瑞金医院确诊的363例原发性Ig AN患者的临床、病理及随访资料。采用免疫散射比浊法检测血清C3水平,根据血清C3水平将患者分为低C3血症组(C3<0.85 g/L)和正常C3组,比较2组患者临床、病理及预后指标。采用酶联免疫吸附法检测血清补体旁路途径相关因子,包括人末端补体复合物(SC5b-9)、C3a、补体H因子(CFH)、B因子(CFB)、I因子(CFI)水平。结果:363例Ig AN患者中伴低C3血症患者共133例(36.6%)。与正常C3组相比,低C3血症组患者镜下血尿比例高、血红蛋白水平低、肾小球滤过率的估算值(e GFR)水平低,肾脏病理表现节段性肾小球硬化比例高。多因素Cox回归显示,低C3血症为Ig AN患者进入终末期肾衰竭的独立危险因素。与正常对照组相比,伴有血C3下降的Ig AN患者C3a、SC5b-9显著升高;而C4、CFH、CFI、CFB显著降低。相较于SC5b-9正常组,血清SC5b-9升高组患者血白蛋白较低,2组其他基线临床主要指标及预后无显著差异。相较于CFH正常组,血清CFH下降组患者年龄较小,但2组其他临床主要指标及预后相仿。结论:伴低C3血症的Ig AN患者临床及病理表现更重,且预后不良。补体旁路途径过度活化存在于部分低C3血症Ig AN患者中,提示补体旁路途径过度活化参与Ig AN的发生与进展。

Objective To investigate the correlation of decreased serum C3 and abnormal activation of the alternative complement pathway with clinicopathological severity and prognosis of Ig A nephropathy（Ig AN）. Methods The clinical,pathological and follow-up data of primary Ig AN patients at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2014 were analyzed retrospectively. Levels of serum C3 were detected by immunoscattering turbidimetry. Patients with C30.85 g/L and C3 ≥0.85 g/L were categorized into the hypo-C3 group and the normal C3 group, respectively. Clinical, pathological manifestations and prognosis between the two groups were compared. Enzyme-linked immunosorbent assay（ ELISA） was used to detect the serum factors involved in alternative complement pathway, including human terminal complement complex（SC5 b-9）, C3 a, complement factor H（CFH）,complement factor B（ CFB） and complement factor I（ CFI）. Results Altogether 363 Ig AN patients were recruited, 133（36.6%） were categorized into the hypo-C3 group. Compared with normal C3 group, patients in hypo-C3 group had higher proportion of microscopic hematuria, lower hemoglobin level and lower estimated glomerular filtration rate（e GFR）, and higher proportion of segmental glomerulosclerosis. Cox regression model showed that decreased serum C3 was an independent risk factor for end-stage renal disease in Ig AN. Compared with normal C3 group, patients in hypo-C3 group had significantly higher levels of C3 a and SC5 b-9, and lower levels of C4, CFH, CFI and CFB. Compared with patients with normal serum SC5 b-9, patients with elevated serum SC5 b-9 had lower serum albumin. Compared with patients with normal serum CFH, patients with decreased serum CFH were younger. There were no significant differences in other clinical indicators and prognosis between normal and abnormal serum SC5 b-9 groups, as well as between normal and abnormal serum CFH groups. Conclusions Ig AN patients with decreased serum C3 had severe clinical and pathological manifestations and poor prognosis. Abnormal activation of alternative complement pathway was involved in some patients with decreased serum C3, suggesting the association between abnormal activation of alternative complement pathway and pathogenesis and progression of Ig AN.