Autoimmunity in Membranous Nephropathy Targets Aldose Reductase and SOD2

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2010 Feb 13

PMID 20150532

Citations 92

Authors

Marco Prunotto

Maria Luisa Carnevali

Giovanni Candiano

Corrado Murtas

Maurizio Bruschi

Emilia Corradini

Antonella Trivelli

Alberto Magnasco

Andrea Petretto

Laura Santucci

Silvia Mattei

Rita Gatti

Francesco Scolari

Peter Kador

Landino Allegri

Gian Marco Ghiggeri

Affiliations

Soon will be listed here.

Abstract

Glomerular targets of autoimmunity in human membranous nephropathy are poorly understood. Here, we used a combined proteomic approach to identify specific antibodies against podocyte proteins in both serum and glomeruli of patients with membranous nephropathy (MN). We detected specific anti-aldose reductase (AR) and anti-manganese superoxide dismutase (SOD2) IgG(4) in sera of patients with MN. We also eluted high titers of anti-AR and anti-SOD2 IgG(4) from microdissected glomeruli of three biopsies of MN kidneys but not from biopsies of other glomerulonephritides characterized by IgG deposition (five lupus nephritis and two membranoproliferative glomerulonephritis). We identified both antigens in MN biopsies but not in other renal pathologies or normal kidney. Confocal and immunoelectron microscopy (IEM) showed co-localization of anti-AR and anti-SOD2 with IgG(4) and C5b-9 in electron-dense podocyte immune deposits. Preliminary in vitro experiments showed an increase of SOD2 expression on podocyte plasma membrane after treatment with hydrogen peroxide. In conclusion, our data support AR and SOD2 as renal antigens of human MN and suggest that oxidative stress may drive glomerular SOD2 expression.

Citing Articles

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