Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia and usually responds well to steroids. However, relapses are frequent, which can require multi-drug therapy with deleterious long-term side effects. In the last decades, different hypotheses on molecular mechanisms underlying INS have been proposed and several lines of evidences strongly indicate a crucial role of the immune system in the pathogenesis of non-genetic INS. INS is traditionally considered a T-cell-mediated disorder triggered by a circulating factor, which causes the impairment of the glomerular filtration barrier and subsequent proteinuria. Additionally, the imbalance between Th17/Tregs as well as Th2/Th1 has been implicated in the pathomechanism of INS. Interestingly, B-cells have gained attention, since rituximab, an anti-CD20 antibody demonstrated a good therapeutic response in the treatment of INS. Finally, recent findings indicate that even podocytes can act as antigen-presenting cells under inflammatory stimuli and play a direct role in activating cellular pathways that cause proteinuria. Even though our knowledge on the underlying mechanisms of INS is still incomplete, it became clear that instead of a traditionally implicated cell subset or one particular molecule as a causative factor for INS, a multi-step control system including soluble factors, immune cells, and podocytes is necessary to prevent the occurrence of INS. This present review aims to provide an overview of the current knowledge on this topic, since advances in our understanding of the immunopathogenesis of INS may help drive new tailored therapeutic approaches forward.

中文翻译：

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免疫系统在特发性肾病综合征中的作用

儿童特发性肾病综合征 (INS) 的特点是大量蛋白尿和低白蛋白血症，通常对类固醇反应良好。然而，复发是频繁的，这可能需要具有有害的长期副作用的多种药物治疗。在过去的几十年中，已经提出了关于 INS 分子机制的不同假设，并且一些证据强烈表明免疫系统在非遗传 INS 发病机制中的关键作用。INS 传统上被认为是由循环因子触发的 T 细胞介导的疾病，它会导致肾小球滤过屏障受损和随后的蛋白尿。此外，Th17/Tregs 以及 Th2/Th1 之间的不平衡与 INS 的发病机制有关。有趣的是，自利妥昔单抗以来，B 细胞受到了关注，抗CD20抗体在INS治疗中表现出良好的治疗反应。最后，最近的研究结果表明，即使是足细胞也可以在炎症刺激下充当抗原呈递细胞，并在激活导致蛋白尿的细胞途径中发挥直接作用。尽管我们对 INS 潜在机制的了解仍然不完整，但很明显，不是传统上涉及的细胞亚群或一个特定分子作为 INS 的致病因素，而是一个多步骤控制系统，包括可溶性因子、免疫细胞和足细胞是防止 INS 发生所必需的。本综述旨在概述有关该主题的当前知识，因为我们对 INS 免疫发病机制的理解的进步可能有助于推动新的定制治疗方法的发展。