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Nephrol Dial Transplant. 2014 Dec;29(12):2334-42. doi: 10.1093/ndt/gfu252. Epub 2014 Jul 25.

Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients.

Author information

1
Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS et Université de Nice-Sophia Antipolis, Valbonne, France Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, Nice, France.
2
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS et Université de Nice-Sophia Antipolis, Valbonne, France.
3
Service d'anatomopathologie, Hôpital Pasteur, Université Nice-Sophia Antipolis, Nice, France.
4
Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France.
5
Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France Service d'anatomopathologie, Hôpital Pasteur, Université Nice-Sophia Antipolis, Nice, France.
6
Service de Néphro-pédiatrie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, Nice, France.
7
Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, Nice, France.

Abstract

BACKGROUND:

The predictive value of anti-M-type phospholipase A2 receptor (PLA2R1) autoantibodies for membranous nephropathy (MN) recurrence after renal transplantation remains controversial.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

PLA2R1 autoantibodies; membranous nephropathy; prognosis; recurrence; transplantation

PMID:
25063424
DOI:
10.1093/ndt/gfu252
[Indexed for MEDLINE]

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