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

Laurence H. Beck, Fernando C. Fervenza, David M. Beck, Ramon G.B. Bonegio, Fahim A. Malik, Stephen B. Erickson, Fernando G. Cosio, Daniel C. Cattran, David J. Salant

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293 Scopus citations

Abstract

Autoantibodies to the M-type phospholipase A2 receptor (PLA 2R) 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-PLA2R 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-PLA2R 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-PLA2R, 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-PLA2R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA2R. In summary, measuring anti-PLA2R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

Original languageEnglish (US)
Pages (from-to)1543-1550
Number of pages8
JournalJournal of the American Society of Nephrology
Volume22
Issue number8
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Nephrology

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    Beck, L. H., Fervenza, F. C., Beck, D. M., Bonegio, R. G. B., Malik, F. A., Erickson, S. B., Cosio, F. G., Cattran, D. C., & Salant, D. J. (2011). Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. Journal of the American Society of Nephrology, 22(8), 1543-1550. https://doi.org/10.1681/ASN.2010111125