TY - JOUR
T1 - Autoimmunity in membranous nephropathy targets aldose reductase and SOD2
AU - Prunotto, Marco
AU - Carnevali, Maria Luisa
AU - Candiano, Giovanni
AU - Murtas, Corrado
AU - Bruschi, Maurizio
AU - Corradini, Emilia
AU - Trivelli, Antonella
AU - Magnasco, Alberto
AU - Petretto, Andrea
AU - Santucci, Laura
AU - Mattei, Silvia
AU - Gatti, Rita
AU - Scolari, Francesco
AU - Kador, Peter
AU - Allegri, Landino
AU - Ghiggeri, Gian Marco
PY - 2010/3
Y1 - 2010/3
N2 - 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) IgG4 in sera of patients with MN. We also eluted high titers of anti-AR and anti-SOD2 IgG4 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 IgG4 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.
AB - 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) IgG4 in sera of patients with MN. We also eluted high titers of anti-AR and anti-SOD2 IgG4 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 IgG4 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.
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U2 - 10.1681/ASN.2008121259
DO - 10.1681/ASN.2008121259
M3 - Article
C2 - 20150532
AN - SCOPUS:77949902393
SN - 1046-6673
VL - 21
SP - 507
EP - 519
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 3
ER -