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Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: Alfa-enolase and borderline antigens.

Research paper by Maurizio M Bruschi, Maria Luisa ML Carnevali, Corrado C Murtas, Giovanni G Candiano, Andrea A Petretto, Marco M Prunotto, Rita R Gatti, Lucia L Argentiero, Riccardo R Magistroni, Giacomo G Garibotto, Francesco F Scolari, Pietro P Ravani, Loreto L Gesualdo, Landino L Allegri, Gian Marco GM Ghiggeri

Indexed on: 07 Jun '11Published on: 07 Jun '11Published in: Journal of Proteomics



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.

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