M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. Export

@article{citeulike:5052669, 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.}, author = {Beck, Laurence H. and Bonegio, Ramon G. and Lambeau, G\'{e}rard and Beck, David M. and Powell, David W. and Cummins, Timothy D. and Klein, Jon B. and Salant, David J.}, citeulike-article-id = {5052669}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa0810457}, citeulike-linkout-1 = {http://content.nejm.org/cgi/content/abstract/361/1/11}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19571279}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19571279}, day = {2}, doi = {10.1056/NEJMoa0810457}, issn = {1533-4406}, journal = {The New England journal of medicine}, keywords = {disease-mechanism, membranous-nephropathy, pathogenesis}, month = {July}, number = {1}, pages = {11--21}, posted-at = {2009-07-04 04:48:30}, priority = {0}, title = {M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.}, url = {http://dx.doi.org/10.1056/NEJMoa0810457}, volume = {361}, year = {2009} }

TY - JOUR ID - citeulike:5052669 L3 - citeulike-article-id:5052669 N2 - 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. IS - 1 JF - The New England journal of medicine SN - 1533-4406 EP - 21 TI - M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. VL - 361 SP - 11 KW - disease-mechanism KW - membranous-nephropathy KW - pathogenesis AU - Beck, Laurence AU - Bonegio, Ramon AU - Lambeau, Gérard AU - Beck, David AU - Powell, David AU - Cummins, Timothy AU - Klein, Jon AU - Salant, David PY - 2009/07/02/ UR - http://dx.doi.org/10.1056/NEJMoa0810457 ER -