The role of the immune system in idiopathic nephrotic syndrome.

IF 2.4 Q1 PEDIATRICS
Agnes Hackl, Seif El Din Abo Zed, Paul Diefenhardt, Julia Binz-Lotter, Rasmus Ehren, Lutz Thorsten Weber
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引用次数: 7

Abstract

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.

Abstract Image

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,这可能需要多种药物治疗,有害的长期副作用。在过去的几十年里,人们对INS的分子机制提出了不同的假设,一些证据强烈表明免疫系统在非遗传性INS的发病机制中起着至关重要的作用。INS传统上被认为是一种由循环因子引发的t细胞介导的疾病,它会导致肾小球滤过屏障的损害和随后的蛋白尿。此外,Th17/Tregs和Th2/Th1之间的失衡与INS的病理机制有关。有趣的是,自从抗cd20抗体利妥昔单抗在治疗INS中表现出良好的治疗反应以来,b细胞已经引起了人们的关注。最后,最近的研究结果表明,即使足细胞也可以在炎症刺激下充当抗原呈递细胞,并在激活引起蛋白尿的细胞通路中发挥直接作用。尽管我们对INS的潜在机制的了解仍然不完整,但很明显,一个包括可溶性因子、免疫细胞和足细胞在内的多步骤控制系统是预防INS发生所必需的,而不是传统的相关细胞亚群或一个特定的分子作为INS的致病因素。这篇综述的目的是对这一主题的当前知识进行概述,因为我们对INS的免疫发病机制的理解的进展可能有助于推动新的定制治疗方法的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
2.20
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