Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: Alfa-enolase and borderline antigens
| Autor: | Gian Marco Ghiggeri, Maria Luisa Carnevali, Marco Prunotto, Andrea Petretto, Pietro Ravani, Loreto Gesualdo, Riccardo Magistroni, Francesco Scolari, Landino Allegri, Rita Gatti, Maurizio Bruschi, Corrado Murtas, Giovanni Candiano, Lucia Argentiero, Giacomo Garibotto |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Glycine-tRNA Ligase Male Pathology medicine.medical_specialty Enolase Kidney Glomerulus Biophysics Complement Membrane Attack Complex Laser Capture Microdissection Biology medicine.disease_cause Kidney Biochemistry Autoantigens Glomerulonephritis Membranous Podocyte Autoimmunity Pathogenesis Autoantibodies Glomerulonephritis Immune system Antigen Peptide Elongation Factor 2 medicine Humans Aged Podocytes Autoantibody Middle Aged medicine.disease medicine.anatomical_structure Immunoglobulin G Phosphopyruvate Hydratase Immunology Female |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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