Background and aims Annexin II mediates anti-dsDNA antibody binding to mesangial cells and downstream inflammatory and fibrotic processes. We investigated the relationship between annexin II-binding IgG and clinical or histological activity in lupus nephritis.

Methods Serial serum samples from 28 patients with Class III/IV±V lupus nephritis were studied. Annexin II-binding IgG level was measured with an in-house ELISA. Glomeruli were isolated from NZBWF1 mice, gene and protein expression of annexin II and its binding protein p11 were investigated by real-time PCR and cytochemical staining respectively. Ultrastructural localization of annexin II was determined by electron microscopy and immunogold staining.

Results Annexin II-binding IgG level was associated with anti-dsDNA level and disease activity 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=0.02), and karyorrhexis/fibrinoid necrosis score (r=0.66, p=0.002) in renal biopsies, and also with the amount of mesangial electron-dense deposit scored semi-quantitatively (r=0.63, p=0.009). Glomerular annexin II and p11 expression increased with disease progression in NZBWF1 mice, and annexin II was found on the surface of mesangial cells and in the mesangial matrix, co-localising with electron-dense deposits.

Conclusions Our data demonstrated an association between annexin II-binding IgG level and clinical/histological disease activity in proliferative lupus nephritis. Co-localization of annexin II with electron-dense deposits suggests a pathogenic role for annexin II.