Patients with membranous nephropathy (MN) and persistent nephrotic syndrome (NS) are at increased risk of -progression to end-stage renal disease. The discovery of -autoantibodies against the podocyte-expressed M-type phospholipase A2 receptor (PLA2R) provided a clear pathophysiological rationale for interventions targeting the B-cell lineage to prevent antibody production and subepithelial immune-complex deposition. The anti-CD20 monoclonal antibodies, rituximab and ofatumumab, are safe and achieve remission of NS in approximately two-thirds of patients with MN. In patients with PLA2R-related MN, remission can be predicted by anti-PLA2R antibody depletion, and faster depletion is associated with earlier reduction of proteinuria and improved nephroprotection. Selective apheresis methods, such as double-filtration plasmapheresis (DFPP), may accelerate the clearance of autoreactive antibodies and at the same time avoid the side effects of plasma-exchange. In this preliminary, explorative, proof-of-concept study, we observed that in patients with PLA2R-related MN, NS and high antibody levels, ofatumumab-induced B-cell depletion followed by DFPP accelerated anti-PLA2R depletion compared to anti-CD20 monotherapy. This therapeutic regimen was safe and well tolerated. These observations may provide the background for controlled trials aimed at formally testing whether the addition of DFPP to anti-CD20 therapy could offer a novel therapeutic option, especially for patients with more severe MN.
Accelerating the Depletion of Circulating Anti-Phospholipase A2 Receptor Antibodies in Patients with Severe Membranous Nephropathy: Preliminary Findings with Double Filtration Plasmapheresis and Ofatumumab / M.A. Podesta, A. Gennarini, V. Portalupi, S. Rota, M.G. Alessio, G. Remuzzi, P. Ruggenenti. - In: NEPHRON JOURNALS. - ISSN 1660-8151. - 144:1(2020 Jan 01), pp. 30-35.
|Titolo:||Accelerating the Depletion of Circulating Anti-Phospholipase A2 Receptor Antibodies in Patients with Severe Membranous Nephropathy: Preliminary Findings with Double Filtration Plasmapheresis and Ofatumumab|
PODESTA', MANUEL ALFREDO (Primo)
REMUZZI, GIUSEPPE (Penultimo) (Corresponding)
|Parole Chiave:||Apheresis; Membranous nephropathy; Ofatumumab; PLA2R|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||1-gen-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1159/000501858|
|Appare nelle tipologie:||01 - Articolo su periodico|