title: Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: Alfa-enolase and borderline antigens.
abstract: The identification of glomerular auto-antigens in idiopathic human membranous glomerulonephritis (MGN) is a crucial step towards the definition of the mechanisms of the disease. Recent 'in vivo' studies demonstrated a heterogeneous composition of glomerular immune-deposits in MGN biopsies only a part of which have been characterized. We studied with a proteomical approach IgGs eluted from laser capture microdissected glomeruli of 8 MGN patients and showed the existence of other three immune proteins in MGN glomeruli (α-enolase, elongation factor 2 and Glycyl Aminoacyl-tRNA Synthetase). One of these, i.e. α-enolase, fulfilled all criteria for being considered an auto-antigen. Specific IgG₁ and IgG₄ reacting with podocyte α-enolase were, in fact, eluted from microdissected glomeruli and Confocal- and Immuno Electron-Microscopy showed co-localization of α-enolase with IgG₄ and C5b-9 in immune-deposits. Serum levels of anti a-enolase IgG4 were determined in 131 MGN patients and were found elevated in 25% of cases. Overall, our data demonstrate that glomerular α-enolase is a target antigen of autoimmunity in human MGN. Circulating anti α-enolase auto-antibodies can be detected in sera of a significant quota of MGN patients. Like other auto-antigens, α-enolase may be implicated in the pathogenesis of human MGN.
authors.affiliation: Division of Nephrology and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Carnevali
authors.forename: Corrado
authors.initials: C
authors.lastname: Murtas
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Marco
authors.initials: M
authors.lastname: Prunotto
authors.forename: Rita
authors.initials: R
authors.lastname: Gatti
authors.forename: Lucia
authors.initials: L
authors.lastname: Argentiero
authors.forename: Riccardo
authors.initials: R
authors.lastname: Magistroni
authors.forename: Giacomo
authors.initials: G
authors.lastname: Garibotto
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000276:immunology; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000276:immunology* / Q000473:pathology; D006032:Glycine-tRNA Ligase / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D020652:Peptide Elongation Factor 2 / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D050199:Podocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G; D020652:Peptide Elongation Factor 2; D010751:Phosphopyruvate Hydratase; D006032:Glycine-tRNA Ligase