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

• Published in: Journal of the American Society of Nephrology Vol. 22; no. 8; pp. 1543 - 1550
• Main Authors: Beck, Laurence H., Fervenza, Fernando C., Beck, David M., Bonegio, Ramon G.B., Malik, Fahim A., Erickson, Stephen B., Cosio, Fernando G., Cattran, Daniel C., Salant, David J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.08.2011
• Subjects: Adult; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal, Murine-Derived - pharmacology; Autoantibodies - chemistry; Biological and medical sciences; Biopsy; Clinical Research; Cohort Studies; Female; Glomerulonephritis; Glomerulonephritis, Membranous - drug therapy; Glomerulonephritis, Membranous - immunology; Humans; Immunologic Factors - pharmacology; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Receptors, Phospholipase A2 - chemistry; Receptors, Phospholipase A2 - immunology; Rituximab; Time Factors; Treatment Outcome; Kidney disease; Antineoplastic agent; Autoimmunity; Nephrology; Urinary system disease; Autoantibody; Rituximab; Monoclonal antibody; Urology; Immunomodulator; Depletion; Treatment; Immunotherapy; Membranous glomerulonephritis; Immunosuppressive agent; Predictive factor
• ISSN: 1046-6673; 1533-3450; 1533-3450
• DOI: 10.1681/ASN.2010111125

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.