Accelerating the Depletion of Circulating Anti-Phospholipase A2 Receptor Antibodies in Patients with Severe Membranous Nephropathy: Preliminary Findings with Double Filtration Plasmapheresis and Ofatumumab

Manuel Alfredo Podestà, Alessia Gennarini, Valentina Portalupi, Stefano Rota, Maria Grazia Alessio, Giuseppe Remuzzi, Piero Ruggenenti

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)30-35
Number of pages6
JournalNephron
Volume144
Issue number1
DOIs
Publication statusPublished - 2020

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Phospholipase A2 Receptors
Membranous Glomerulonephritis
Plasmapheresis
Nephrotic Syndrome
Antibodies
B-Lymphocytes
Podocytes
Blood Component Removal
Plasma Exchange
Cell Lineage
Antigen-Antibody Complex
Proteinuria
Autoantibodies
Chronic Kidney Failure
Antibody Formation
Therapeutics
Monoclonal Antibodies
ofatumumab

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Accelerating the Depletion of Circulating Anti-Phospholipase A2 Receptor Antibodies in Patients with Severe Membranous Nephropathy : Preliminary Findings with Double Filtration Plasmapheresis and Ofatumumab. / Podestà, Manuel Alfredo; Gennarini, Alessia; Portalupi, Valentina; Rota, Stefano; Alessio, Maria Grazia; Remuzzi, Giuseppe; Ruggenenti, Piero.

In: Nephron, Vol. 144, No. 1, 2020, p. 30-35.

Research output: Contribution to journalArticle

Podestà, Manuel Alfredo ; Gennarini, Alessia ; Portalupi, Valentina ; Rota, Stefano ; Alessio, Maria Grazia ; Remuzzi, Giuseppe ; Ruggenenti, Piero. / Accelerating the Depletion of Circulating Anti-Phospholipase A2 Receptor Antibodies in Patients with Severe Membranous Nephropathy : Preliminary Findings with Double Filtration Plasmapheresis and Ofatumumab. In: Nephron. 2020 ; Vol. 144, No. 1. pp. 30-35.
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