Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy

The M-type phospholipase A2 receptor (PLA 2 R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA 2 R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA 2 R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA 2 R expression was strongly positive in glomeruli, and in 60 of these patients PLA 2 R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA 2 R autoantibodies were faintly positive for PLA 2 R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA 2 R. Thus, increased staining for PLA 2 R in glomeruli of renal biopsies tightly correlates with the presence of PLA 2 R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy.