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Abstract：
BACKGROUND: Activation of the complement pathway by immune complexes is a key feature of systemic lupus erythematosus (SLE) and SLE glomerulonephritis, which translates into low levels of C3 and C4 during active disease. C3 glomerulonephritis (C3GN) is part of a broader group of rare renal diseases, the C3 glomerulopathies, characterized by prominent C3 accumulation in the glomeruli with minimal to no immunoglobulin (Ig) deposition secondary to dysregulation of the alternative pathway of the complement system. Distinguishing lupus nephritis from other complement-mediated kidney disorders, including C3GN, represents a diagnostic challenge with potential therapeutic implications.
METHODS: We report an unusual case of a 55-year-old woman with SLE and previous biopsy-proven class IV lupus nephritis, subsequently diagnosed with C3GN. Furthermore, we review the available literature published from January 2010-March 2021 on the clinical features and management of C3GN in the setting of SLE.
RESULTS: In addition to our case, very few reports exist in the literature regarding C3GN in association with SLE. The underlying pathogenic mechanism of C3GN consists of dysregulation of the alternative pathway of the complement system, either due to genetic variation in complement-related genes or to acquired autoantibodies targeting C3 or C5 convertases; the latter mechanism could explain the occurrence of C3GN in the setting of autoimmune diseases, although it was not definitively identified in our patient or others with SLE. Similar to some of the previous reports, after suboptimal renal response on mycophenolate mofetil and rituximab, our patient has been successfully treated with eculizumab, thus far with >50% improvement in proteinuria.
CONCLUSIONS: C3GN represents an additional mechanism of renal injury in SLE mediated by alternative complement pathway dysregulation. Although rare, patients with SLE and persistent proteinuria with very low C3 would benefit from expedited renal biopsy to evaluate for C3GN as well as genetic testing, since this entity could require a different therapeutic approach.
METHODS: We report an unusual case of a 55-year-old woman with SLE and previous biopsy-proven class IV lupus nephritis, subsequently diagnosed with C3GN. Furthermore, we review the available literature published from January 2010-March 2021 on the clinical features and management of C3GN in the setting of SLE.
RESULTS: In addition to our case, very few reports exist in the literature regarding C3GN in association with SLE. The underlying pathogenic mechanism of C3GN consists of dysregulation of the alternative pathway of the complement system, either due to genetic variation in complement-related genes or to acquired autoantibodies targeting C3 or C5 convertases; the latter mechanism could explain the occurrence of C3GN in the setting of autoimmune diseases, although it was not definitively identified in our patient or others with SLE. Similar to some of the previous reports, after suboptimal renal response on mycophenolate mofetil and rituximab, our patient has been successfully treated with eculizumab, thus far with >50% improvement in proteinuria.
CONCLUSIONS: C3GN represents an additional mechanism of renal injury in SLE mediated by alternative complement pathway dysregulation. Although rare, patients with SLE and persistent proteinuria with very low C3 would benefit from expedited renal biopsy to evaluate for C3GN as well as genetic testing, since this entity could require a different therapeutic approach.
摘要：
背景：免疫复合物激活补体途径是系统性红斑狼疮（SLE）和SLE肾小球肾炎的关键特征，在活动性疾病期间转化为低水平的C3和C4。C3肾小球肾炎（C3GN）是一组更广泛的罕见肾脏疾病的一部分，C3肾小球疾病，其特征在于肾小球中明显的C3积累，次要是补体系统替代途径失调的免疫球蛋白（Ig）沉积。将狼疮性肾炎与其他补体介导的肾脏疾病区分开来，包括C3GN,代表了具有潜在治疗意义的诊断挑战。
方法：我们报告了一例55岁的女性SLE和之前经活检证实的IV类狼疮性肾炎的罕见病例，随后诊断为C3GN。此外，我们回顾了2010年1月至2021年3月发表的关于SLE患者C3GN的临床特征和治疗的现有文献.
结果：除了我们的案例，文献中关于C3GN与SLE相关的报道很少。C3GN的潜在致病机制包括补体系统替代途径的失调，由于补体相关基因的遗传变异或针对C3或C5转化酶的获得性自身抗体;后一种机制可以解释C3GN在自身免疫性疾病中的发生，尽管在我们的患者或其他患有SLE的患者中尚未明确发现。类似于以前的一些报道，霉酚酸酯和利妥昔单抗的肾脏反应欠佳后，我们的患者已成功接受了依库珠单抗治疗，到目前为止，蛋白尿改善>50%。
结论：C3GN代表了替代补体途径失调介导的SLE肾损伤的另一种机制。虽然罕见，患有SLE和持续性蛋白尿且C3非常低的患者将受益于快速肾活检以评估C3GN以及基因检测，因为这个实体可能需要不同的治疗方法。
方法：我们报告了一例55岁的女性SLE和之前经活检证实的IV类狼疮性肾炎的罕见病例，随后诊断为C3GN。此外，我们回顾了2010年1月至2021年3月发表的关于SLE患者C3GN的临床特征和治疗的现有文献.
结果：除了我们的案例，文献中关于C3GN与SLE相关的报道很少。C3GN的潜在致病机制包括补体系统替代途径的失调，由于补体相关基因的遗传变异或针对C3或C5转化酶的获得性自身抗体;后一种机制可以解释C3GN在自身免疫性疾病中的发生，尽管在我们的患者或其他患有SLE的患者中尚未明确发现。类似于以前的一些报道，霉酚酸酯和利妥昔单抗的肾脏反应欠佳后，我们的患者已成功接受了依库珠单抗治疗，到目前为止，蛋白尿改善>50%。
结论：C3GN代表了替代补体途径失调介导的SLE肾损伤的另一种机制。虽然罕见，患有SLE和持续性蛋白尿且C3非常低的患者将受益于快速肾活检以评估C3GN以及基因检测，因为这个实体可能需要不同的治疗方法。
