title: Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy.
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/m(2)) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximab-treated 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.
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and Unit of Nephrology, Azienda Ospedaliera Ospedale Papa Giovanni XXIII, Bergamo, Italy;
authors: Piero
authors: P
authors: Ruggenenti
authors: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche UMR_S1155, Paris, France; Sorbonne Universités, Universitè Pierre and Marie Curie University, Paris 06, Paris, France; and.
authors: Hanna
authors: H
authors: Debiec
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Barbara
authors: B
authors: Ruggiero
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Antonietta
authors: A
authors: Chianca
authors: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche UMR_S1155, Paris, France; Sorbonne Universités, Universitè Pierre and Marie Curie University, Paris 06, Paris, France; and.
authors: Timothee
authors: T
authors: Pellé
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Flavio
authors: F
authors: Gaspari
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Flavio
authors: F
authors: Suardi
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Elena
authors: E
authors: Gagliardini
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Silvia
authors: S
authors: Orisio
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and.
authors: Ariela
authors: A
authors: Benigni
authors: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche UMR_S1155, Paris, France; Sorbonne Universités, Universitè Pierre and Marie Curie University, Paris 06, Paris, France; and Assistance Publique-Hôpitaux de Paris, Department of Nephrology and Dialysis, Tenon Hospital, Paris, France.
authors: Pierre
authors: P
authors: Ronco
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, and Unit of Nephrology, Azienda Ospedaliera Ospedale Papa Giovanni XXIII, Bergamo, Italy; Giuseppe.remuzzi@marionegri.it.
authors: Giuseppe
authors: G
authors: Remuzzi
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D007155:Immunologic Factors; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D000069283:Rituximab
keywords: glomerulonephritis; membranous nephropathy; nephrotic syndrome; polymorphisms; primary; proteinuria