Figure 1.

Intramolecular epitope spreading in PLA2R-associated membranous nephropathy. The progression of intramolecular epitope spreading in PLA2R-associated membranous nephropathy (MN). Initially, autoantibodies target the CysR domain of the PLA2R receptor on podocytes. As the disease advances, antibody recognition extends to additional domains, including CTLD1, CTLD7, and CTLD8, correlating with an increase in antibody titers and disease severity. This spreading drives podocyte injury, foot process effacement, and disruption of the glomerular filtration barrier, resulting in proteinuria. External immune triggers may accelerate this process, worsening clinical outcomes and reducing the likelihood of remission. (Created in BioRender.com).