Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; John Walls Renal Unit, University Hospitals of Leicester National Health Service Trust, Leicester, UK.
Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford University, Stanford, California, USA.
Kidney Int. 2024 Nov;106(5):806-818. doi: 10.1016/j.kint.2024.08.012. Epub 2024 Sep 7.
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.
增殖诱导配体 (APRIL) 是肿瘤坏死因子超家族细胞因子的一个关键成员，在 B 细胞存活、增殖和 Ig 类别转换中发挥核心作用。最近，由于 APRIL 和相关细胞因子 B 细胞激活因子在几种肾小球疾病中的重要作用，人们对它们的兴趣日益增加。APRIL 的治疗性抑制代表了一种潜在有吸引力的免疫调节方法，它可能消除自身免疫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完好，例如记忆 B 细胞功能和对疫苗的反应，与 B 细胞耗竭策略形成对比。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，并概述了新兴的临床研究数据，研究了 APRIL 抑制，重点关注 IgA 肾病，其中 APRIL 抑制剂的临床开发处于最先进的阶段。
