期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 25, 期 11, 页码 2483-2498出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2013090987
关键词
-
资金
- Cinque per mille of Personal Income Tax (IRPEF)-Finanziamento della ricerca sanitaria
- Italian Ministry of Health Ricerca Corrente contributo per la ricerca intramuraria
- Institute Giannina Gaslini
- Renal Child Foundation
- Fondazione La Nuova Speranza (Progetto integrato per la definizione dei meccanismi implicati nella glomerulo sclerosi focale)
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 alpha-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of a-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-alpha-enolase (>15 mg/L) IgG2 and/or anti-annexin Al (>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-alpha-enolase/low anti-annexin Al IgG2 and patients with low anti-alpha-enolase/high anti-annexin Al IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-alpha-enolase IgG2 recognized specific epitopes of alpha-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human alpha-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against alpha-enolase and annexin Al predominate in the glomerulus and can be detected in serum.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据