Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease

Lahme K, Sachs W, Froembling S, Loreth D, Böttcher-Dierks V, Neumann K, Hann FM, Arkan N, Brehler M, Reichelt J, Sgries A, Surmann K, Gaffling S, Adler MR, Sáez PJ, Wedekind U, Lampert A, Tasika E, Saftig P, Conze C, Thünauer R, Skuza S, Neitzel K, Zielinski S, Brand J, Bonn S, Michalik S, Völker U, Zimmermann M, Wiech T, Meyer TN, Fester L, Meyer-Schwesinger C (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cell Elsevier

DOI: 10.1016/j.cell.2025.11.010

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.

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Heinrich-Pette-Institut (HPI), Leibniz-Institut für Experimentelle Virologie / Heinrich Pette Institute – Leibniz Institute for Experimental Virology DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Asklepios Kliniken DE Germany (DE) HistoDigital (HiD) UG DE Germany (DE)

How to cite

APA:

Lahme, K., Sachs, W., Froembling, S., Loreth, D., Böttcher-Dierks, V., Neumann, K.,... Meyer-Schwesinger, C. (2025). Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease. Cell. https://doi.org/10.1016/j.cell.2025.11.010

MLA:

Lahme, Karen, et al. "Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease." Cell (2025).

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