PLA 2 R Autoantibodies and PLA 2 R Glomerular Deposits in Membranous Nephropathy

Abstract

1. Membranous nephropathy is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. 2. In the rat model described by Heymann in 1959, the target antigen of antibodies is megalin, a multiligand receptor expressed in the rat glomerulus, but absent from the human glomerulus. 3. In the past few years, two major antigens have been identified in human membranous nephropathy. The first is neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of membranous nephropathy that occur in newborns from NEP-deficient mothers. The second is the M-type phospholipase A2 receptor (PLA(2) R), the first autoantigen identified in idiopathic membranous nephropathy in the adult. Megalin, NEP and PLA(2) R are all expressed on the podocyte surface where they can serve as targets for circulating antibodies, which leads to in situ immune complex formation, complement activation and proteinuria. 4. In addition to podocyte antigens, we recently showed that some patients with childhood membranous nephropathy had both circulating cationic bovine serum albumin (BSA) and anti-BSA antibodies, with BSA being present in immune deposits. This suggests that food antigens may be involved in membranous nephropathy through charge-dependent binding to anionic glomerular capillary wall and in situ formation of immune complexes.