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

Bruschi, M., Sinico, R., Moroni, G., Pratesi, F., Migliorini, P., Galetti, M., et al. (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 [10.1681/ASN.2013090987].

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

SINICO, RENATO ALBERTO
Secondo
;
Trezzi, B;
2014

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
Articolo in rivista - Articolo scientifico
GN; immunology and pathology; lupus nephritis; Adolescent; Adult; Animals; Annexin A1; Autoantibodies; Biomarkers, Tumor; Biopsy; DNA-Binding Proteins; Female; Humans; Immunoglobulin G; Kidney Glomerulus; Lupus Nephritis; Male; Mice, Inbred BALB C; Mice, Inbred MRL lpr; Mice, SCID; Middle Aged; Phosphopyruvate Hydratase; Proteomics; Tumor Suppressor Proteins; Young Adult; Nephrology
English
2014
25
11
2483
2498
none
Bruschi, M., Sinico, R., Moroni, G., Pratesi, F., Migliorini, P., Galetti, M., et al. (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 [10.1681/ASN.2013090987].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/139221
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