Annexin II-binding Immunoglobulins in Patients with Lupus Nephritis and their Correlation with Disease Manifestations

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in NZBWF1/J mice. Annexin II-binding immunoglobulins in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis was significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG, and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG/IgM level was associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM level correlated with histological Activity Index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG/IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the gl...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research