A proliferation-inducing ligand (APRIL) is a key member of the tumor necrosis factor superfamily of cytokines and plays a central role in B-cell survival, proliferation, and Ig class switching. Recently, there has been increasing interest in the role of APRIL and the related cytokine B-cell activating factor in several glomerular diseases, because of their importance in the above processes. The therapeutic inhibition of APRIL represents a potentially attractive immunomodulatory approach that may abrogate deleterious host immune responses in autoimmune diseases while leaving other important functions of humoral immunity intact, such as memory B-cell function and responses to vaccination, in contrast to B-cell–depleting strategies. In this review, we describe the physiological roles of APRIL in B-cell development and their relevance to glomerular diseases, and outline emerging clinical trial data studying APRIL inhibition, with a focus on IgA nephropathy where the clinical development of APRIL inhibitors is in its most advanced stage.

中文翻译：

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靶向 APRIL 治疗肾小球疾病


增殖诱导配体 （APRIL） 是细胞因子肿瘤坏死因子超家族的关键成员，在 B 细胞存活、增殖和 Ig 类别转换中起着核心作用。最近，由于 APRIL 和相关的细胞因子 B 细胞活化因子在上述过程中的重要性，人们对它们在几种肾小球疾病中的作用越来越感兴趣。APRIL 的治疗性抑制代表了一种可能有吸引力的免疫调节方法，它可以消除自身免疫性疾病中有害的宿主免疫反应，同时保持体液免疫的其他重要功能，例如记忆 B 细胞功能和对疫苗接种的反应，与 B 细胞耗竭策略相反。在这篇综述中，我们描述了 APRIL 在 B 细胞发育中的生理作用及其与肾小球疾病的相关性，并概述了研究 APRIL 抑制的新临床试验数据，重点是 APRIL 抑制剂临床开发处于最晚期的 IgA 肾病。