Developments in the scientific understanding of lupus

Abstract

Systemic lupus erythematosus is a systemic autoimmune disease characterized by the production of antinuclear antibodies (ANAs). Recent research into human and murine lupus suggests that disease susceptibility results from genetic polymorphisms regulating immune responses as well as impairing the clearance of apoptotic cells. Because the products of dead cells, including nucleic acids, have immunologic activity, this situation can promote antigen-driven ANA responses. Furthermore, immune complexes of ANAs can drive the production of proinflammatory cytokines, inducing the 'interferon signature', and intensifying disease. Together, these findings point to new genetic and immunologic markers of disease as well as targets for new therapies.

Figure 1

Model of key events in SLE pathogenesis. Dying cells release nucleic acid, including DNA, which binds immunoglobulin to form circulating immune complexes. These immune complexes can directly mediate cell damage by binding to target tissues, for example in the glomerulus. Immune complexes also bind Fc receptors on plasmacytoid dendritic cells, and in concert with RAGE receptors and TLR9, promote expression and release of IFN-α. IFN-α, in turn, promotes multiple immune system aberrations including the upregulation of B cells, T cells, and dendritic and endothelial cells. RAGE, receptor for advanced glycation end-products; SLE, systemic lupus erythematosus; TLR, Toll-like receptor.