Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI

Maurizio Bruschi, Renato Alberto Sinico, Gabriella Moroni, Federico Pratesi, Paola Migliorini, Maricla Galetti, Corrado Murtas, Angela Tincani, Michael Madaio, Antonella Radice, Franco Franceschini, Barbara Trezzi, Laura Bianchi, Agata Giallongo, Rita Gatti, Regina Tardanico, Andrea Scaloni, Chiara D'Ambrosio, Maria Luisa Carnevali, Piergiorgio MessaPietro Ravani, Giancarlo Barbano, Beatrice Bianco, Alice Bonanni, Francesco Scolari, Alberto Martini, Giovanni Candiano, Landino Allegri, Gian Marco Ghiggeri

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Abstract

Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-α-enolase/low anti-annexin AI IgG2 and patients with low anti-α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12months of therapy for LN. Anti-α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum.

Original languageEnglish (US)
Pages (from-to)2483-2498
Number of pages16
JournalJournal of the American Society of Nephrology
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2014

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ASJC Scopus subject areas

  • Nephrology

Cite this

Bruschi, M., Sinico, R. A., Moroni, G., Pratesi, F., Migliorini, P., Galetti, M., Murtas, C., Tincani, A., Madaio, M., Radice, A., Franceschini, F., Trezzi, B., Bianchi, L., Giallongo, A., Gatti, R., Tardanico, R., Scaloni, A., D'Ambrosio, C., Carnevali, M. L., ... Ghiggeri, G. M. (2014). Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI. Journal of the American Society of Nephrology, 25(11), 2483-2498. https://doi.org/10.1681/ASN.2013090987