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

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.

• Authors: Hanna Debiec, Melanie Hanoy, Arnaud Francois, Dominique Guerrot, Sophie Ferlicot, Catherine Johanet, Pierre Aucouturier, Michel Godin, Pierre Ronco
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 23 Issue 12 Pg. 1949-54 (Dec 2012) ISSN: 1533-3450 [Electronic] United States
• PMID: 23123401 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Receptors, Phospholipase A2

Topics

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