Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor

J Am Soc Nephrol. 2012 Dec;23(12):1949-54. doi: 10.1681/ASN.2012060577. Epub 2012 Nov 2.

Abstract

Up to 80% of patients with idiopathic membranous nephropathy have non-complement-fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). Membranous nephropathy recurs in approximately 40% of patients after kidney transplantation, but the mechanism is unknown. Here, we describe a patient with recurrent membranous nephropathy 13 days after kidney transplantation whose graft biopsy specimen showed granular staining for C3, C5b-9, C1q, and IgG3κ; electron microscopy revealed subepithelial nonorganized deposits. A search for hematologic disorders was negative. Retrospective evaluation of a biopsy sample from the native kidney revealed a similar pattern: monotypic IgG3κ deposits together with C3, C1q, and C5b-9. Glomerular deposits contained PLA2R in both the graft and the native kidney, suggesting that the recurrence was the result of circulating anti-PLA2R antibodies binding to PLA2R antigen expressed on donor podocytes. Confocal analysis of anti-PLA2R and antihuman IgG3 showed co-localization, and the patient had IgG3κ-restricted circulating anti-PLA2R antibodies. Treatment with rituximab stabilized both proteinuria and serum creatinine, and circulating anti-PLA2R became undetectable. In summary, this case of recurrent membranous nephropathy in a graft suggests that circulating monoclonal anti-PLA2R IgG3κ caused the disease and activated complement by the classic pathway.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glomerulonephritis, Membranous / immunology*
  • Humans
  • Immunoglobulin G / physiology*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Postoperative Complications / immunology*
  • Receptors, Phospholipase A2 / immunology*
  • Recurrence
  • Transplantation, Homologous / immunology

Substances

  • Immunoglobulin G
  • Receptors, Phospholipase A2