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.

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Bruschi M,Carnevali ML,Murtas C,Candiano G,Petretto A,Prunotto M,Gatti R,Argentiero L,Magistroni R,Garibotto G,Scolari F,Ravani P,Gesualdo L,Allegri L,Ghiggeri GM

doi

10.1016/j.jprot.2011.05.021

subject

Has Abstract

pub_date

2011-09-06 00:00:00

pages

2008-17

issue

10

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(11)00212-0

journal_volume

74

pub_type

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