Abstract

Primary membranous nephropathy (also known as idiopathic membranous nephropathy, IMN) is an organ specific autoimmune kidney disease characterized by the development of immune complex deposits in the sub-epithelial spaces, podocyte effacement and glomerular capillary wall thickening in the later stages. Clinical studies have demonstrated that over 70% of patients with IMN possess circulating autoimmune antibodies specifically targeting the phospholipase A2 receptor (PLA2R) on the surface of podocytes. The autoantibodies only bind to the extracellular portion of PLA2R under the non-reducing condition, indicating that the epitope in PLA2R is conformational requiring specific disulfide bonds to maintain its structure. We recently have successfully located the dominant epitope in PLA2R to the extreme N-terminus of the receptor. This finding has opened a new direction for understanding the pathogenesis of anti-PLA2R autoantibody induced IMN and offered a strong basis for developing sensitive clinical assays for IMN diagnosis and prognosis, and potentially, new therapeutic approaches for IMN treatment.

Keywords: Apheresis column, enzyme-linked immunosorbent assay (ELISA), epitope, idiopathic membranous nephropathy (IMN), immunotolerance therapy, integrin α3β1, kidney, mechanism, pathogenesis, phospholipase A2 receptor (PLA2R).

Graphical Abstract