Anti-Phospholipase A(2) Receptor Autoantibody: A New Biomarker for Primary Membranous Nephropathy

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 A(2) receptor (PLA(2)R) on the surface of podocytes. The autoantibodies only bind to the extracellular portion of PLA(2)R under the non-reducing condition, indicating that the epitope in PLA(2)R is conformational requiring specific disulfide bonds to maintain its structure. We recently have successfully located the dominant epitope in PLA(2)R to the extreme N-terminus of the receptor. This finding has opened a new direction for understanding the pathogenesis of anti-PLA(2)R 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.