Anti-PLA2R1 IgG-mediated podocyte PLA2R1 cleavage drives glomerular subepithelial immune complex deposition in membranous nephropathy - PubMed
4 hours ago
- #membranous nephropathy
- #immune complex deposition
- #PLA2R1
- Anti-PLA2R1 IgG in membranous nephropathy (MN) triggers podocyte PLA2R1 cleavage, leading to immune complex deposition in the glomerular basement membrane (GBM).
- The study used human podocytes and HEK293 cells to show that MN(P+) serum or purified anti-PLA2R1 IgG increases PLA2R1 C-terminal fragment and soluble ectodomain (ECD), blocked by ADAM10/17 inhibitors.
- PLA2R1-ECD binds to collagen IV/laminin in the GBM, anchoring immune deposits, with PLA2R1-ECD enriched in GBM deposits in MN(P+) biopsies.
- The findings explain how circulating anti-PLA2R1 IgG generates GBM-anchored immune complexes from podocyte antigens, linking serum antibodies to glomerular deposits in MN.