Rituximab-induced depletion of anti-PLA 2R autoantibodies predicts response in membranous nephropathy

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

Research output: Contribution to journalArticle

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Abstract

Autoantibodies to the M-type phospholipase A 2 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-PLA 2R 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 2R 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 2R, 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 2R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA 2R. In summary, measuring anti-PLA 2R 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

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Membranous Glomerulonephritis
Autoantibodies
Proteinuria
Immunoassay
Phospholipases A
Therapeutics
B-Lymphocytes
Biomarkers
Western Blotting
Rituximab
Antibodies
Serum

ASJC Scopus subject areas

  • Nephrology

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Rituximab-induced depletion of anti-PLA 2R autoantibodies predicts response in membranous nephropathy. / Beck, Laurence H.; Fervenza, Fernando Custodio; Beck, David M.; Bonegio, Ramon G B; Malik, Fahim A.; Erickson, Stephen B.; Cosio, Fernando G; Cattran, Daniel C.; Salant, David J.

In: Journal of the American Society of Nephrology, Vol. 22, No. 8, 2011, p. 1543-1550.

Research output: Contribution to journalArticle

Beck, LH, Fervenza, FC, Beck, DM, Bonegio, RGB, Malik, FA, Erickson, SB, Cosio, FG, Cattran, DC & Salant, DJ 2011, 'Rituximab-induced depletion of anti-PLA 2R autoantibodies predicts response in membranous nephropathy', Journal of the American Society of Nephrology, vol. 22, no. 8, pp. 1543-1550. https://doi.org/10.1681/ASN.2010111125
Beck, Laurence H. ; Fervenza, Fernando Custodio ; Beck, David M. ; Bonegio, Ramon G B ; Malik, Fahim A. ; Erickson, Stephen B. ; Cosio, Fernando G ; Cattran, Daniel C. ; Salant, David J. / Rituximab-induced depletion of anti-PLA 2R autoantibodies predicts response in membranous nephropathy. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 8. pp. 1543-1550.
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