title: 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.affiliation: Institut National de la Santé et de la Recherche Médicale UMR_S 702, Paris, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
authors.forename: Melanie
authors.initials: M
authors.lastname: Hanoy
authors.forename: Arnaud
authors.initials: A
authors.lastname: Francois
authors.forename: Dominique
authors.initials: D
authors.lastname: Guerrot
authors.forename: Sophie
authors.initials: S
authors.lastname: Ferlicot
authors.forename: Catherine
authors.initials: C
authors.lastname: Johanet
authors.forename: Pierre
authors.initials: P
authors.lastname: Aucouturier
authors.forename: Michel
authors.initials: M
authors.lastname: Godin
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
mesh_terms: D015433:Glomerulonephritis, Membranous / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology*; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012008:Recurrence; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D054507:Receptors, Phospholipase A2