Cell · 2025
Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Lahme Karen, Sachs Wiebke, Froembling Sarah, Loreth Desiree, Böttcher-Dierks Vincent, Neumann Katrin, Hann Frederik-Michael, Arkan Nick, Brehler Michael, Reichelt Julia, Sgries Antonia, Surmann Kristin, Gaffling Simone, Adler Marie R, Sáez Pablo J, Wedekind Uta, Lampert Alina, Tasika Elena, Saftig Paul, Conze Christian, Thünauer Roland, Skuza Sinah, Neitzel Karen, Zielinski Stephanie, Brand Johannes, Bonn Stefan, Michalik Stephan, Völker Uwe, Zimmermann Marina, Wiech Thorsten, Meyer Tobias N, Fester Lars, Meyer-Schwesinger Catherine
Аннотация
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.