BACKGROUND The pathophysiology of the leading cause of pediatric acute nephritis, acute postinfectious GN, including mechanisms of the pathognomonic transient complement activation, remains uncertain. It shares clinicopathologic features with C3 glomerulopathy, a complement-mediated glomerulopathy that, unlike acute postinfectious GN, has a poor prognosis. METHODS This retrospective study investigated mechanisms of complement activation in 34 children with acute postinfectious GN and low C3 level at onset. We screened a panel of anticomplement protein autoantibodies, carried out related functional characterization, and compared results with those of 60 children from the National French Registry who had C3 glomerulopathy and persistent hypocomplementemia. RESULTS All children with acute postinfectious GN had activation of the alternative pathway of the complement system. At onset, autoantibodies targeting factor B (a component of the alternative pathway C3 convertase) were found in a significantly higher proportion of children with the disorder versus children with hypocomplementemic C3 glomerulopathy (31 of 34 [91%] versus 4 of 28 [14%], respectively). In acute postinfectious GN, anti-factor B autoantibodies were transient and correlated with plasma C3 and soluble C5b-9 levels. We demonstrated that anti-factor B antibodies enhance alternative pathway convertase activity in vitro, confirming their pathogenic effect. We also identified crucial antibody binding sites on factor B, including one correlated to disease severity. CONCLUSIONS These findings elucidate the pathophysiologic mechanisms underlying acute postinfectious GN by identifying anti-factor B autoantibodies as contributing factors in alternative complement pathway activation. At onset of a nephritic syndrome with low C3 level, screening for anti-factor B antibodies might help guide indications for kidney biopsy to avoid misdiagnosed chronic glomerulopathy, such as C3 glomerulopathy, and to help determine therapy.

中文翻译：

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儿童抗因子B抗体和急性感染后GN。

背景技术小儿急性肾炎，急性感染后GN的主要病因的病理生理学，包括病理组学短暂补体激活的机制，仍是不确定的。它与C3肾小球病具有临床病理特征，C3肾小球病是一种补体介导的肾小球病，与急性感染后GN不同，其预后较差。方法这项回顾性研究调查了34例急性感染后GN和C3水平低的儿童的补体激活机制。我们筛选了一组抗补体蛋白自身抗体，进行了相关的功能表征，并将结果与​​法国国家注册处的60名患有C3肾小球病和持续性补体不足的儿童进行了比较。结果所有患有急性感染性GN的儿童均激活了补体系统的替代途径。发病时，与低互补性C3肾小球肾病患儿相比，该疾病患儿中靶向因子B（替代途径C3转化酶的组成部分）的自身抗体的比例明显更高（34例中有31例[91％]，而28例中有4例[14％] ]， 分别）。在急性感染后GN中，抗因子B自身抗体是短暂的，并与血浆C3和可溶性C5b-9水平相关。我们证明了抗因子B抗体在体外增强了替代途径转化酶的活性，证实了其致病作用。我们还确定了因子B上的关键抗体结合位点，包括一个与疾病严重程度相关的位点。结论这些发现通过确定抗因子B自身抗体是替代补体途径激活的促成因素，阐明了急性感染后GN的病理生理机制。在C3水平低的肾病综合征发作时，筛查抗B因子抗体可能有助于指导肾脏活检的指征，从而避免误诊为C3肾小球病等慢性肾小球病，并帮助确定治疗方法。