title: Association of anti-PLA₂R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy.
abstract: BACKGROUND
  The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate.
  
  
  METHODS
  This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA.
  
  
  RESULTS
  In total, 48 patients (37 men) were included. The median age was 55 years (range, 34-75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98-3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab-positive patients, treatment resulted in a rapid decrease of antibodies: median anti-PLA2R-ab, 428 U/ml (range, 41-16,260 U/ml) at baseline and 24 U/ml (range, 0-505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003).
  
  
  CONCLUSIONS
  These data suggest that in PLA2R-ab-positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course.
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands; and Anneke.vanderWoude-Bech@radboudumc.nl.
authors.forename: Anneke P
authors.initials: AP
authors.lastname: Bech
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands; and.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hofstra
authors.affiliation: Manchester Institute of Nephrology and Transplantation, Manchester, United Kingdom.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Brenchley
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands; and.
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007166:Immunosuppressive Agents; D054507:Receptors, Phospholipase A2; D003520:Cyclophosphamide; D009173:Mycophenolic Acid
keywords: anti-PLA2R antibodies; disease course; immunosuppressive; membranous nephropathy; therapy