Annexin II-binding immunoglobulin level correlates with renal histological features in lupus nephritis

Abstract

BACKGROUND: Annexin II on the surface of mesangial cells mediates anti-dsDNA antibody binding and downstream inflammatory and fibrotic processes in lupus nephritis. We investigated the relationship between annexin II-binding immunoglobulins and renal histology in lupus nephritis. METHODS: Archived serial serum samples from 28 patients with Class III/IV lupus nephritis were retrieved, and annexin II-binding immunoglobulin level was measured with an in-house ELISA. Glomeruli were isolated from NZBWF1 mice, and annexin II gene and protein expression was investigated by real-time PCR and cytochemical staining respectively. Ultrastructural localization of annexin II was determined by immunogold staining and electron microscopy. RESULTS: Associations between serum annexin II-binding IgG level, anti-dsDNA level, and disease activity were observed in 42% of lupus nephritis patients. Annexin II-binding IgG level correlated with activity index (r=0.44, p=0.04), leukocyte infiltration score (r=0.52, p=0.01), and karyorrhexis/fibrinoid necrosis score (r=0.66, p=0.002) as stated in the patients’ renal biopsy reports, and also the semi-quantitative mesangial electron-dense deposit score (r=0.63, p=0.009). Glomerular annexin II expression increased with active nephritis and decreased with glomerulosclerosis in NZBWF1 mice. Annexin II expression co-localized with electron-dense deposits in the mesangium, along the glomerular basement membrane and around podocytes. CONCLUSIONS: The association between annexin II-binding IgG level and histological features of severe nephritis and the co-localization of annexin II with electron-dense deposits both implicate annexin II in the pathogenesis of lupus nephritis. Funding: Government Support ‑ Non-U.S.