title: Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy.
abstract: The phospholipase A(2) receptor (PLA(2)R) is the major target antigen in idiopathic membranous nephropathy. The technique for measuring antibodies against PLA(2)R and the relationship between antibody titer and clinical characteristics are not well established. Here, we measured anti-PLA(2)R (aPLA(2)R) antibody titer and subclass in a well defined cohort of 117 Caucasian patients with idiopathic membranous nephropathy and nephrotic-range proteinuria using both indirect immunofluorescence testing (IIFT) and ELISA. We assessed agreement between tests and correlated antibody titer with clinical baseline parameters and outcome. In this cohort, aPLA(2)R antibodies were positive in 74% and 72% of patients using IIFT and ELISA, respectively. Concordance between both tests was excellent (94% agreement, κ=0.85). Among 82 aPLA(2)R-positive patients, antibody titer significantly correlated with baseline proteinuria (P=0.02). Spontaneous remissions occurred significantly less frequently among patients with high antibody titers (38% versus 4% in the lowest and highest tertiles, respectively; P<0.01). IgG4 was the dominant subclass in the majority of patients. Titers of IgG4, but not IgG1 or IgG3, significantly correlated with the occurrence of spontaneous remission (P=0.03). In summary, these data show high agreement between IIFT and ELISA assessments of aPLA(2)R antibody titer and highlight the pathogenetic role of these antibodies, especially the IgG4 subclass, given the observed relationships between aPLA(2)R titer, baseline proteinuria, and outcome.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Nephrology, Nijmegen, The Netherlands. j.hofstra@nier.umcn.nl
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hofstra
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
authors.forename: Colin D
authors.initials: CD
authors.lastname: Short
authors.forename: Timotheé
authors.initials: T
authors.lastname: Pellé
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mathieson
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.forename: Paul E
authors.initials: PE
authors.lastname: Brenchley
authors.forename: Jack F
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000145:classification; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology / Q000276:immunology; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012075:Remission, Spontaneous; D051437:Renal Insufficiency / Q000209:etiology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D054507:Receptors, Phospholipase A2