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.
Anti-Phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy / P. Ruggenenti, H. Debiec, B. Ruggiero, A. Chianca, T. Pellé, F. Gaspari, F. Suardi, E. Gagliardini, S. Orisio, A. Benigni, P. Ronco, G. Remuzzi. - In: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. - ISSN 1046-6673. - 26:10(2015 Oct), pp. 2545-2558.
|Titolo:||Anti-Phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy|
REMUZZI, GIUSEPPE (Ultimo)
|Parole Chiave:||glomerulonephritis; membranous nephropathy; nephrotic syndrome; polymorphisms; primary; proteinuria; nephrology|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||ott-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1681/ASN.2014070640|
|Appare nelle tipologie:||01 - Articolo su periodico|