Anti-dsDNA antibodies and resident renal cells - Their putative roles in pathogenesis of renal lesions in lupus nephritis.

Lupus nephritis affects up to 70% of patients with systemic lupus erythematosus and is an important treatable cause of kidney failure. Cardinal features of lupus nephritis include loss of self-tolerance, production of autoantibodies, immune complex deposition and immune-mediated injury to the kidney, resulting in increased cell proliferation, apoptosis, and induction of inflammatory and fibrotic processes that destroy normal nephrons. The production anti-dsDNA antibodies is a cardinal feature in lupus and their level correlates with disease activity. In addition to the formation of immune complexes thereby triggering complement activation, how anti-dsDNA antibodies home to the kidney and induce pathological processes in the renal parenchyma remain to be fully elucidated. Data from our laboratory and other investigators show that the properties of anti-dsDNA antibodies vary between patients and change over time, and that anti-dsDNA antibodies could bind directly to integral cell surface molecules such as annexin II or α-actinin, or indirectly through chromatin material deposited on the cell surface. The binding of anti-dsDNA antibodies to mesangial cells and proximal renal tubular epithelial cells triggers downstream inflammatory and fibrotic pathways, which include the activation of the PKC and MAPK signaling pathways, increased secretion of pro-inflammatory cytokines and matrix protein deposition that contribute to pathological processes in the renal parenchyma.