Anti-Phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy

Piero Ruggenenti, Hanna Debiec, Barbara Ruggiero, Antonietta Chianca, Timothee Pellé, Flavio Gaspari, Flavio Suardi, Elena Gagliardini, Silvia Orisio, Ariela Benigni, Pierre Ronco, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m2) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximabtreated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P ≤ 0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P ≤ 0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti- PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.

Original languageEnglish
Pages (from-to)2545-2558
Number of pages14
JournalJournal of the American Society of Nephrology
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Anti-Phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy'. Together they form a unique fingerprint.

Cite this