Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy

J Am Soc Nephrol. 2018 Feb;29(2):401-408. doi: 10.1681/ASN.2017070734. Epub 2017 Nov 7.


The phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). At baseline, the epitope profile (CysR, CysRC1, CysRC7, or CysRC1C7) did not correlate with age, sex, time from diagnosis, proteinuria, or serum albumin, but epitope spreading strongly correlated with PLA2R1-Ab titer (P<0.001). Ten (58.8%) of the 17 patients who had epitope spreading at baseline and were treated with rituximab showed reversal of epitope spreading at month 6. In adjusted analysis, epitope spreading at baseline was associated with a decreased remission rate at month 6 (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.72; P=0.02) and last follow-up (median, 23 months; odds ratio, 0.14; 95% confidence interval, 0.03 to 0.64; P=0.01), independently from age, sex, baseline PLA2R1-Ab level, and treatment group. We propose that epitope spreading at baseline be considered in the decision for early therapeutic intervention in patients with primary membranous nephropathy.

Keywords: Immunology and pathology; clinical immunology; immunosuppression; membranous nephropathy; randomized controlled trials.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Autoantigens / immunology
  • Epitopes / drug effects
  • Female
  • Glomerulonephritis, Membranous / blood*
  • Glomerulonephritis, Membranous / drug therapy
  • Humans
  • Immunologic Factors / therapeutic use
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Receptors, Phospholipase A2 / immunology*
  • Remission Induction
  • Rituximab / therapeutic use


  • Autoantibodies
  • Autoantigens
  • Epitopes
  • Immunologic Factors
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2
  • Rituximab