汉堡肾脏健康中心Catherine Meyer-Schwesinger团队的研究开发出了自身抗体触发足细胞膜出芽驱动自身免疫性肾脏疾病。相关论文于2025年12月4日发表于国际顶尖学术期刊《细胞》杂志上。
全世界每10个人中就有1个人患有慢性肾脏疾病，肾脏中被称为足细胞的特殊血液过滤细胞的损伤起着至关重要的作用。在膜性肾病（MN）中，循环自身抗体攻击足细胞足突（FPs）上的蛋白质，破坏肾脏的滤过屏障。他们的研究表明，这些自身抗体触发足细胞FP质膜上抗原-自身抗体聚集体的形成。这些聚集体形成茎状囊泡，称为自身免疫球蛋白触发的细胞外囊泡（AIT-EVs），释放到尿液中。AIT-EVs携带疾病引导自身抗体，其靶抗原，必需FP蛋白和疾病相关应激源，代表清除免疫复合物（ICs）和废物的机制。
然而，它们的过量释放会导致FP消失和足细胞功能障碍。在MN患者中，尿AIT-EVs对应于肾小球尿腔聚集物。富集AIT-EVs可以检测和监测病原性自身抗体，为自身免疫性肾脏疾病的诊断和治疗提供了一种无创方法。
附：英文原文
Title: Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease
Author: Karen Lahme, Wiebke Sachs, Sarah Froembling, Desiree Loreth, Vincent Bttcher-Dierks, Katrin Neumann, Frederik-Michael Hann, Nick Arkan, Michael Brehler, Julia Reichelt, Antonia Sgries, Kristin Surmann, Simone Gaffling, Marie R. Adler, Pablo J. Sáez, Uta Wedekind, Alina Lampert, Elena Tasika, Paul Saftig, Christian Conze, Roland Thünauer, Sinah Skuza, Karen Neitzel, Stephanie Zielinski, Johannes Brand, Stefan Bonn, Stephan Michalik, Uwe Vlker, Marina Zimmermann, Thorsten Wiech, Tobias N. Meyer, Lars Fester, Catherine Meyer-Schwesinger
Issue&Volume: 2025-12-04
Abstract: Chronic kidney disease affects 1 in 10 people worldwide, with damage to specialized blood filter cells of the kidney, called podocytes, playing a critical role. In membranous nephropathy (MN), a major cause of nephrotic syndrome, circulating autoantibodies attack proteins on podocyte foot processes (FPs), damaging the kidney’s filtration barrier. Our study shows that these autoantibodies trigger the formation of antigen-autoantibody aggregates on the podocyte FP plasma membrane. These aggregates bud off as stalked vesicles, termed autoimmunoglobulin-triggered extracellular vesicles (AIT-EVs), which are released into the urine. AIT-EVs carry disease-causing autoantibodies, their target antigens, essential FP proteins, and disease-associated stressors representing a mechanism for removing immune complexes (ICs) and waste. However, their excessive release leads to FP effacement and podocyte dysfunction. In MN patients, urinary AIT-EVs correspond to glomerular urinary-space aggregates. Enriching AIT-EVs enables detection and monitoring of pathogenic autoantibodies, suggesting a non-invasive approach for autoimmune kidney disease diagnosis and therapy.
DOI: 10.1016/j.cell.2025.11.010
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01306-6