Serum Levels of Anti-Annexin II Antibodies Correlate with Disease Manifestations in Lupus Nephritis

Abstract

INTRODUCTION AND AIMS: We have previously demonstrated that annexin II is a cross-reactive antigen on the surface of mesangial cells that mediate anti-dsDNA antibody binding and down-stream inflammatory processes. In this study, we investigated the relationship between serum anti-annexin II activity and clinical parameters of disease. METHODS: Serial serum samples from 23 patients with biopsy-proven severe proliferative lupus nephritis were included in this study. Serum samples from age- and sex-matched non-lupus glomerular disease and healthy individuals were used as controls. Serum anti-annexin II activity was determined by “in-house” ELISA and clinical parameters such as serum levels of IgG, anti-dsDNA antibodies, creatinine and C3 were measured by commercial assays. RESULTS: A total of 487 serum samples were obtained from patients with lupus nephritis, which comprised 97 and 390 samples from patients during active disease and remission respectively. Serum levels of anti-annexin II activity were significantly higher in patients with lupus nephritis compared with controls (P<0.01), and were higher in patients with active disease compared to remission in 15 out of 23 (65%) patients. Sero-positivity rate for anti-annexin II IgG was 20.3%, 5.3%, and 3.1% in patients with lupus nephritis, non-lupus glomerular diseases, and healthy controls respectively (P<0.001 for all). Anti-annexin II levels correlated with the level of anti-dsDNA antibodies (r=0.26, P<0.001), total IgG (r=0.45, P<0.0001), and serum creatinine (r=0.45, P<0.001), and inversely correlated with C3 level (r=-0.31, P<0.001). CONCLUSIONS: Our data demonstrate that IgG anti-annexin II titre correlates with serological and clinical markers of disease activity in lupus nephritis.