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Abstract: SA-PO956

Monoclonal Characterization of Autoreactive PLA2R1 Antibody Responses in Membranous Nephropathy (MN)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials


  • Reinhard, Linda, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Montagner, Sara, Novartis AG, Basel, Basel-Stadt, Switzerland
  • Marchant, Martine, Novartis AG, Basel, Basel-Stadt, Switzerland
  • Iazeolla, Mariavittoria, Novartis AG, Basel, Basel-Stadt, Switzerland
  • Lavoisier, Alexandra, Novartis AG, Basel, Basel-Stadt, Switzerland
  • Traggiai, Elisabetta, Novartis AG, Basel, Basel-Stadt, Switzerland
  • Hoxha, Elion, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Membranous nephropathy (MN) is caused by circulating antibodies, which in 70-80% of cases are directed against PLA2R1. The CysR domain of the PLA2R1 is the immune dominant domain and all patients with PLA2R1-induced MN exhibit antibodies against this domain of the protein. Today, all treatment options for MN are unspecific concerning the molecular disease pathogenesis.


We isolated PBMCs from patients with PLA2R1-induced MN. Using tagged PLA2R1, PLA2R1-specific B cells were isolated and the corresponding B cell receptors were cloned, in order to produce monoclonal human PLA2R1-antibodies (PLA2R1-mAb) corresponding to autoantibodies from patients with MN. The inhibitory potential of these PLA2R1-mAb for human PLA2R1-antibody binding to PLA2R1 was tested in vitro by competition ELISA using 60 sera from patients with PLA2R1-induced MN and in vivo in a rat model, which expresses the human PLA2R1 (hPLA2R1) specifically on podocytes.


In total, four PLA2R1-mAb were cloned from PLA2R1-specific B cells from patients with MN and bound epitopes on the CysR domain. Every PLA2R1-mAb was tested for its inhibitory capability using 60 PLA2R1-antibody positive sera from patients with PLA2R1-induced MN. The PLA2R1-mAb inhibited the PLA2R1-antibody binding capacity of the patient sera by 45% - 96%. The inhibitory effect of each PLA2R1-mAb was independent of the PLA2R1-antibody level of the sera; i.e. the PLA2R1-mAb with the highest inhibition of 96% exhibited a PLA2R1-antibody inhibition of 95%, 96% and 96%, when sera with PLA2R1-anitbody level of 40-79 U/ml, 80-250 U/ml and > 250 U/ml were used, respectively. PLA2R1-mAb were injected into a rat with podocyte-specific hPLA2R1-expression prior to passive transfer of human PLA2R1-antibodies from patients with MN. This PLA2R1-mAb led to an inhibition of PLA2R1-antibody binding by 80% in vivo.


We report for the first time the characterization of human monoclonal antibodies specific for PLA2R1 derived from memory B cells of MN patients. Cloned autoantibodies showed strong inhibition of PLA2R1 autoantibody binding both in vitro and in vivo, opening the possibility of a potential PLA2R1 epitope specific treatment.


  • Commercial Support – Novartis, Basel, Switzerland