Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease
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.
Authors
- Roland Thünauer
- Elena Tasika
- Marina Zimmermann (ORCID: https://orcid.org/0000-0002-2666-5997)
- Thorsten Wiech (ORCID: https://orcid.org/0000-0003-4053-1474)
- Johannes Brand (ORCID: https://orcid.org/0000-0001-7954-9853)
- Stefan Bonn (ORCID: https://orcid.org/0000-0003-4366-5662)
- Tobias Meyer (ORCID: https://orcid.org/0000-0003-4339-3804)
- Stephanie Zielinski
- Paul Säftig (ORCID: https://orcid.org/0000-0003-2637-7052)
- Desirée Loreth (ORCID: https://orcid.org/0000-0003-0827-149X)
- Karen L. Neitzel
- Simone Gaffling (ORCID: https://orcid.org/0000-0002-7811-6180)
- Sarah Froembling
- Wiebke Sachs
- Katrin Neumann (ORCID: https://orcid.org/0000-0002-3858-3171)
- Christian Conze (ORCID: https://orcid.org/0000-0002-8849-1064)
- Lars Fester (ORCID: https://orcid.org/0009-0005-3588-5333)
- Angelika Lampert (ORCID: https://orcid.org/0000-0001-6319-6272)
- Sinah Skuza
- Kristin Surmann (ORCID: https://orcid.org/0009-0009-7305-3457)
- Catherine Meyer‐Schwesinger (ORCID: https://orcid.org/0000-0003-1511-5188)
- Uta Wedekind
- Stephan Michalik (ORCID: https://orcid.org/0000-0002-6550-0132)
- Uwe Völker (ORCID: https://orcid.org/0000-0002-5689-3448)
- Michael Brehler (ORCID: https://orcid.org/0000-0002-4663-6587)
- Karen Lahme
- Vincent Böttcher-Dierks
- Julia Reichelt (ORCID: https://orcid.org/0000-0001-7283-2592)
- Pablo J. Sáez (ORCID: https://orcid.org/0000-0003-0521-9426)
- Marie R. Adler
- Antonia Sgries
- Frederik-Michael Hann
- Nick Arkan
Institutions
- University of Bonn (DE)
- Leibniz Institute of Virology (LIV) (DE)
- Universität Hamburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Universitätsmedizin Greifswald (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Universitätsklinikum Erlangen (DE)
- MSH Medical School Hamburg – University of Applied Sciences and Medical University (DE)
- Arkana Laboratories (US)
- Institute of Pathology Celle (DE)
- Institute of Bioinformatics and Systems Biology (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Asklepios Klinik Barmbek (DE)
- Centre for Structural Systems Biology (DE)
Publication Details
- Journal
- Cell
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1016/j.cell.2025.11.010
- Citations
- 5
- Primary Topic
- Renal Diseases and Glomerulopathies
- Type
- article
- Field-Weighted Citation Impact
- 7.15