title: Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients.
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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Barbara
authors: B
authors: Seitz-Polski
authors: Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS et Université de Nice-Sophia Antipolis, Valbonne, France.
authors: Christine
authors: C
authors: Payré
authors: Service d'anatomopathologie, Hôpital Pasteur, Université Nice-Sophia Antipolis, Nice, France.
authors: Damien
authors: D
authors: Ambrosetti
authors: Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France.
authors: Laetitia
authors: L
authors: Albano
authors: Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France Service d'anatomopathologie, Hôpital Pasteur, Université Nice-Sophia Antipolis, Nice, France.
authors: Elisabeth
authors: E
authors: Cassuto-Viguier
authors: Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France.
authors: Marine
authors: M
authors: Berguignat
authors: Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France.
authors: Ahmed
authors: A
authors: Jeribi
authors: Service de Néphro-pédiatrie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, Nice, France.
authors: Marie-Christine
authors: MC
authors: Thouret
authors: Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, Nice, France.
authors: Ghislaine
authors: G
authors: Bernard
authors: Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, Nice, France.
authors: Sylvia
authors: S
authors: Benzaken
authors: Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS et Université de Nice-Sophia Antipolis, Valbonne, France.
authors: Gérard
authors: G
authors: Lambeau
authors: Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, Nice, France.
authors: Vincent L M
authors: VL
authors: Esnault
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000378:metabolism*; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D054507:Receptors, Phospholipase A2
keywords: PLA2R1 autoantibodies; membranous nephropathy; prognosis; recurrence; transplantation