Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy

TLDR

Autoantibodies to the M‑type phospholipase A2 receptor are highly specific for idiopathic membranous nephropathy, yet no early biomarkers exist to predict response to rituximab therapy. We investigated whether anti‑PLA2R levels correlate with immunologic activity and could predict treatment response faster than proteinuria. We quantified anti‑PLA2R by Western blot immunoassay in serial serum samples from 35 rituximab‑treated patients across two cohorts. In 71 % of patients, anti‑PLA2R antibodies declined or disappeared within 12 months of rituximab, and this immunologic response predicted higher remission rates and preceded proteinuria changes, indicating that serial antibody measurement can forecast therapeutic outcomes.

Abstract

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.