Anti-dsDNA Antibodies Bind to Mesangial Annexin II in Lupus Nephritis

作者: Susan Yung , Kwok Fan Cheung , Qing Zhang , Tak Mao Chan

DOI: 10.1681/ASN.2009080805

关键词:

摘要: Production of anti-dsDNA antibodies is a hallmark lupus nephritis, but how these deposit in organs and elicit inflammatory damage remains unknown. In this study, we sought to identify antigens on the surface human mesangial cells (HMC) that mediate binding subsequent pathogenic processes. We isolated from patients with nephritis by affinity chromatography. used multiple methods characterize plasma membrane fraction crossreacted antibodies. found annexin II mediated HMC. After cell surface, were internalized into cytoplasm nucleus. This also led induction IL-6 secretion synthesis, through activation p38 MAPK, JNK, AKT. Binding correlated disease activity nephritis. Glomerular expression severity colocalized IgG C3 deposits both murine Gene silencing HMC reduced antibody partially decreased secretion. summary, our data demonstrate mediates cells, contributing pathogenesis interaction provides potential target for therapeutic intervention.

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