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. Kidney International (2012) 82, 797-804; doi:10.1038/ki.2012.209; published online 6 June 2012