Blog entry by Meguid El Nahas
Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients.
The predictive value of anti-M-type phospholipase A2 receptor (PLA2R1) autoantibodies for membranous nephropathy (MN) recurrence after renal transplantation remains controversial.
Our aim was to monitor anti-PLA2R1 IgG4 activity using a sensitive enzyme-linked immunosorbent assay in 15 kidney transplant recipients with MN, and to test the correlation between antibody titres and MN recurrence.
Five patients never exhibited anti-PLA2R1 antibodies, and one of them relapsed. Ten patients (67%) had IgG4 anti-PLA2R1 antibodies at the time of transplantation and during follow-up. The presence of IgG4 anti-PLA2R1 antibodies at the time of kidney transplantation does not imply MN recurrence (P = 0.600, n = 15). However, a positive IgG4 anti-PLA2R1 activity during follow-up (>Month 6) was a significant risk factor for MN relapse (P = 0.0048, n = 10). Indeed, four patients had persistent IgG4 anti-PLA2R1 activity after transplantation and relapsed. Among them, one was successfully treated with rituximab. Another had persistently high IgG4 anti-PLA2R1 activity and exhibited a histological relapse but no proteinuria while on treatment with renin-angiotensin system inhibitors. In contrast, the six other patients who did not relapse exhibited a decrease of their IgG4 anti-PLA2R1 activity following transplant immunosuppression, including two with proteinuria due to biopsy-proven differential diagnoses. A weak transplant immunosuppressive regimen was also a risk factor of MN recurrence (P = 0.0048, n = 10). Indeed, the six patients who received both an induction therapy and a combined treatment with calcineurin inhibitors/mycophenolate exhibited a decrease of IgG4 anti-PLA2R1 activity and did not relapse, while the four patients who did not receive this strong immunosuppressive treatment association had persistently high IgG4 anti-PLA2R1 activity and relapsed.
The monitoring of IgG4 anti-PLA2R1 titres during follow-up helps to predict MN recurrence, and a strong immunosuppressive treatment of anti-PLA2R1 positive patients may prevent recurrence.
This very interesting observation adds to the evolving knowledge related to IMN and the pathogenic role of anti-PLA2R1 autoantibody.
It encourages the practice of screening potential transplant recipient with a history of IMN for anti-PLA2R1, as the titres of this autoantibody prior to transplantation may guide the immunosuppressive regimen used not only to induce successful induction of tolerability of the allograft but also to suppress anti-PLA2R1 titre, thus preventing, or at least decreasing the risk, of IMN recurrence in the allograft.
A similar approach has been advocated for approaching renal transplantation in aptients with FSGS at higher risk of recurrence in the allograft where screening for, and possibly monitoring, suPAR (soluble urokinase-type plasminogen activator receptor) levels may guide management.
Finally, it would be interesting to know if allograft ischemia and DGF, or even ACR, were associated with a higher incidence of IMN recurrence as damage to the allograft podocytes may expose the antigenic epitopes that trigger the re-emergence of anti-PLA2R1 and the subsequent IMN.
As to the management of the patients who have recurrent IMN with high circulating titres of anti-PLA2R1, a previous report suggested a good response to Rituximab (anti-CD20) therapy, with decreased proteinuria, stabilisation of allograft function and disappearance of the autoantibody.