M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.
Laurence H. Beck,Ramon G. Bonegio,Gérard Lambeau,David M. Beck,David W. Powell,Timothy D. Cummins,Jon B. Klein,David J. Salant +7 more
TLDR
A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA(2)R, indicating that PLA( 2)R is a major antigen in this disease.Abstract:
BACKGROUND Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown. METHODS We performed Western blotting of protein extracts from normal human glomeruli with serum samples from patients with idiopathic or secondary membranous nephropathy or other proteinuric or autoimmune diseases and from normal controls. We used mass spectrometry to analyze the reactive protein bands and confirmed the identity and location of the target antigen with a monospecific antibody. RESULTS Serum samples from 26 of 37 patients (70%) with idiopathic but not secondary membranous nephropathy specifically identified a 185-kD glycoprotein in nonreduced glomerular extract. Mass spectrometry of the reactive protein band detected the M-type phospholipase A 2 receptor (PLA 2 R). Reactive serum specimens recognized recombinant PLA 2 R and bound the same 185-kD glomerular protein as did the monospecific anti-PLA 2 R antibody. Anti-PLA 2 R autoantibodies in serum samples from patients with membranous nephropathy were mainly IgG4, the predominant immunoglobulin subclass in glomerular deposits. PLA 2 R was expressed in podocytes in normal human glomeruli and colocalized with IgG4 in immune deposits in glomeruli of patients with membranous nephropathy. IgG eluted from such deposits in patients with idiopathic membranous nephropathy, but not in those with lupus membranous or IgA nephropathy, recognized PLA 2 R. CONCLUSIONS A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA 2 R. PLA 2 R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA 2 R is a major antigen in this disease.read more
Citations
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Evolving importance of kidney disease: from subspecialty to global health burden
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KDIGO Clinical Practice Guideline for Glomerulonephritis
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Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis
Changli Wei,Shafic El Hindi,Jing Li,Alessia Fornoni,Nelson Goes,Junichiro Sageshima,Dony Maiguel,S. Ananth Karumanchi,Hui-Kim Yap,Moin A. Saleem,Qing-Yin Zhang,Boris Nikolic,Abanti Chaudhuri,Pirouz Daftarian,Eduardo Salido,Armando Torres,Moro O. Salifu,Minnie M. Sarwal,Franz Schaefer,Christian Morath,Vedat Schwenger,Martin Zeier,Vineet Gupta,David M. Roth,Maria Pia Rastaldi,George W. Burke,Phillip Ruiz,Jochen Reiser +27 more
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IgG4-related disease
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Thrombospondin Type-1 Domain-Containing 7A in Idiopathic Membranous Nephropathy
Nicola M. Tomas,Laurence H. Beck,Catherine Meyer-Schwesinger,Barbara Seitz-Polski,Hong Ma,Gunther Zahner,Guillaume Dolla,Elion Hoxha,Udo Helmchen,Anne-Sophie Dabert-Gay,Delphine Debayle,Michael L. Merchant,Jon B. Klein,David J. Salant,Rolf A.K. Stahl,Gérard Lambeau +15 more
TL;DR: In the authors' cohort, 15 of 154 patients with idiopathic membranous nephropathy had circulating autoantibodies to THSD7A but not to PLA2R1, a finding that suggests a distinct subgroup of patients with this condition.
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