BACKGROUND C3 nephritic factors, i.e. autoantibodies that stabilize the C3 convertase of the alternative pathway are the most frequent acquired abnormality in C3 glomerulopathy and primary immunoglobulin-mediated membranoproliferative GN (Ig-MPGN). METHODS Our study included 27 patients with C3 glomerulopathy (n=21) or Ig-MPGN (n=6), of whom 78% were children at disease onset. At the time of sampling, 13/19 (68%) patients with low C3 levels and 8/8 (100%) patients with normal C3 levels were positive for C3 nephritic factors by haemolytic assay. Using novel Luminex assays, we performed a screening for IgG that recognize and affect the formation and/or the stabilization of the alternative pathway C3 convertase (C3bBb). RESULTS Using Luminex assays, an increase in C3bBb formation and/or stabilization was observed in the presence of IgG from 18/27 patients, including 9 with a double-function, 6 only enhancing the C3bBb formation, and 3 that exclusively stabilized C3bBb. All patients presenting a formation and stabilization function had a low C3 level, versus 55% without this double-function. The level of C3bBb formation correlated to the plasmatic C3 but not sC5b-9 levels. The stabilization of C3bBb did not correlate with C3 or sC5b-9 levels. At the last follow-up, 5/27 patients (19%) reached kidney failure after a median delay of 87 [52,119] months. The patients positive for double-function anti-C3bBb antibodies had a 5-year kidney survival of 70% compared to 100% in those negative (P=0.02). CONCLUSIONS Our findings highlight the association of the dual function of C3bBb formation and stabilization with severe C3 consumption and poor kidney survival in C3 glomerulopathy and Ig-MPGN.

中文翻译：

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抗 C3bBb 自身抗体和 C3 肾小球病表型的功能表征。


背景 C3 肾炎因子，即稳定替代途径的 C3 转化酶的自身抗体是 C3 肾小球病和原发性免疫球蛋白介导的膜增生性 GN （Ig-MPGN） 中最常见的获得性异常。方法 我们的研究包括 27 例 C3 肾小球病 （n=21） 或 Ig-MPGN （n=6） 患者，其中 78% 是发病儿童。采样时，溶血试验显示 13/19 例 （68%） C3 水平低的患者和 8/8 （100%） C3 水平正常的患者 C3 肾炎因子阳性。使用新型 Luminex 检测，我们对识别并影响替代途径 C3 转化酶 （C3bBb） 的形成和/或稳定的 IgG 进行了筛选。结果使用 Luminex 测定，在 IgG 存在下观察到 18/27 名患者的 C3bBb 形成和/或稳定增加，其中 9 名具有双重功能，6 名仅增强 C3bBb 形成，3 名仅稳定 C3bBb。所有表现出形成和稳定功能的患者都有较低的 C3 水平，而没有这种双重功能的患者为 55%。C3bBb 形成的水平与质 C3 相关，但与 sC5b-9 水平无关。C3bBb 的稳定与 C3 或 sC5b-9 水平无关。在最后一次随访中，5/27 例患者 （19%） 在中位延迟 87 [52,119] 个月后达到肾衰竭。双功能抗 C3bBb 抗体阳性患者的 5 年肾脏生存率为 70%，而阴性患者的 5 年肾脏生存率为 100% （P = 0.02）。结论 我们的研究结果强调了 C3bBb 形成和稳定的双重功能与 C3 肾小球病和 Ig-MPGN 中严重的 C3 消耗和不良肾脏存活率的关联。