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

被引：95

作者：

Bruschi, Maurizio ^{[1
,2
]}

Carnevali, Maria Luisa ^{[4
]}

Murtas, Corrado ^{[4
]}

Candiano, Giovanni ^{[1
,2
]}

Petretto, Andrea ^{[3
]}

Prunotto, Marco ^{[1
,2
]}

Gatti, Rita ^{[5
]}

Argentiero, Lucia ^{[4
]}

Magistroni, Riccardo ^{[6
]}

Garibotto, Giacomo ^{[7
]}

Scolari, Francesco ^{[8
]}

Ravani, Pietro ^{[10
]}

Gesualdo, Loreto ^{[9
]}

Allegri, Landino ^{[4
]}

Ghiggeri, Gian Marco ^{[1
,2
]}

机构：

[1] G Gaslini Children Hosp, Lab Pathophysiol Uremia, I-16148 Genoa, Italy

[2] G Gaslini Children Hosp, Div Nephrol, I-16148 Genoa, Italy

[3] G Gaslini Children Hosp, Expt & Clin Immunol Lab, Mass Spectrometry Core Facil, I-16148 Genoa, Italy

[4] Dept Clin Med Nephrol & Hlth Sci, Parma, Italy

[5] Univ Parma, Dept Expt Med, Sect Histol, I-43100 Parma, Italy

[6] Univ Modena, Chair Nephrol, I-41100 Modena, Italy

[7] Univ Genoa, Chair Nephrol, I-16126 Genoa, Italy

[8] Univ Brescia, Chair Nephrol, I-25121 Brescia, Italy

[9] Univ Foggia, Chair Nephrol, Foggia, Italy

[10] Univ Calgary, Div Nephrol, Calgary, AB, Canada

来源：

JOURNAL OF PROTEOMICS | 2011年 / 74卷 / 10期

关键词：

Autoimmune glomerulonephritis; Renal auto-antigen; Circulating auto-antibodies; Membranous glomerulonephritis; alpha-enolase; Proteomics; ANTIENDOTHELIAL CELL ANTIBODIES; TRANSFER-RNA-SYNTHETASE; HEYMANN NEPHRITIS; PLASMINOGEN BINDING; NEPHROTIC SYNDROME; PROTEOME ANALYSIS; RAT-KIDNEY; NEPHROPATHY; GP330; MYOSITIS;

D O I：

10.1016/j.jprot.2011.05.021

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (alpha-enolase, elongation factor 2 and Glycyl Aminoacyl-tRNA Synthetase). One of these, i.e. alpha-enolase, fulfilled all criteria for being considered an auto-antigen. Specific IgG(1) and IgG(4) reacting with podocyte alpha-enolase were, in fact, eluted from microdissected glomeruli and Confocal- and Immuno Electron-Microscopy showed co-localization of alpha-enolase with IgG(4) and C5b-9 in immune-deposits. Serum levels of anti alpha-enolase IgG(4) were determined in 131 MGN patients and were found elevated in 25% of cases. Overall, our data demonstrate that glomerular alpha-enolase is a target antigen of autoimmunity in human MGN. Circulating anti alpha-enolase auto-antibodies can be detected in sera of a significant quota of MGN patients. Like other auto-antigens, alpha-enolase may be implicated in the pathogenesis of human MGN. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：2008 / 2017

页数：10

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