Autoimmunity in membranous nephropathy targets aldose reductase and SOD2

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

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154 Scopus citations

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) 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.

Original languageEnglish (US)
Pages (from-to)507-519
Number of pages13
JournalJournal of the American Society of Nephrology
Volume21
Issue number3
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Nephrology

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    Prunotto, M., Carnevali, M. L., Candiano, G., Murtas, C., Bruschi, M., Corradini, E., Trivelli, A., Magnasco, A., Petretto, A., Santucci, L., Mattei, S., Gatti, R., Scolari, F., Kador, P., Allegri, L., & Ghiggeri, G. M. (2010). Autoimmunity in membranous nephropathy targets aldose reductase and SOD2. Journal of the American Society of Nephrology, 21(3), 507-519. https://doi.org/10.1681/ASN.2008121259