M-Type Phospholipase A2 Receptor as Target Antigen in Idiopathic Membranous Nephropathy

In this study of patients with membranous nephropathy, serum samples from 70% of patients with idiopathic, but not secondary, membranous nephropathy were found to have antibodies against a 185-kD glycoprotein in nonreduced glomerular extracts, identified as the M-type phospholipase A 2 receptor (PLA 2 R). PLA 2 R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA 2 R is a major antigen in this disease. Phospholipase A 2 receptor (PLA 2 R) is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that it is a major antigen in this disease. Idiopathic membranous nephropathy, a common cause of the nephrotic syndrome in adults, is an organ-specific autoimmune disease. Despite extensive investigation, a target antigen has been elusive. Studies of membranous nephropathy in a rat model (Heymann's nephritis) established that the subepithelial immune deposits that characterize the disease are formed in situ, as a result of capping and shedding of the target antigen, megalin, from the basal surface of podocytes when it forms a complex with circulating antimegalin antibodies. 1 – 8 Although megalin is not expressed on human podocytes, we hypothesized that a similar process, albeit with an unknown antigen, is operative in . . .