Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy

J Am Soc Nephrol. 2011 Aug;22(8):1543-50. doi: 10.1681/ASN.2010111125. Epub 2011 Jul 22.


Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Autoantibodies / chemistry
  • Biopsy
  • Cohort Studies
  • Female
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology*
  • Humans
  • Immunologic Factors / pharmacology*
  • Male
  • Middle Aged
  • Receptors, Phospholipase A2 / chemistry
  • Receptors, Phospholipase A2 / immunology*
  • Rituximab
  • Time Factors
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Immunologic Factors
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2
  • Rituximab