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.
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Journal of the American Society of Nephrology, American Society of Nephrology, 2012, 23 (12), pp.1949-54. 〈10.1681/ASN.2012060577〉
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Hanna Debiec, Melanie Hanoy, Arnaud Francois, Dominique Guerrot, Sophie Ferlicot, et al.. Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor.. Journal of the American Society of Nephrology, American Society of Nephrology, 2012, 23 (12), pp.1949-54. 〈10.1681/ASN.2012060577〉. 〈inserm-00919065〉

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