title: Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.
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.
authors.affiliation: Department of Medicine, Section of Nephrology, Boston University School of Medicine, Boston, Massachusetts, USA. lhbeckjr@bu.edu
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Beck
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: David M
authors.initials: DM
authors.lastname: Beck
authors.forename: Ramon G B
authors.initials: RG
authors.lastname: Bonegio
authors.forename: Fahim A
authors.initials: FA
authors.lastname: Malik
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Erickson
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Cosio
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Cattran
authors.forename: David J
authors.initials: DJ
authors.lastname: Salant
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000737:chemistry; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D001323:Autoantibodies / Q000737:chemistry; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D054507:Receptors, Phospholipase A2 / Q000737:chemistry / Q000276:immunology*; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D000069283:Rituximab