The immune response to cell death in SLE

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antinuclear antibodies (ANA). These antibodies target a wide variety of antigens whose presence in an immunologically active form may result from cell death processes that cause their translocation and release from cells. As indicated by in vivo model systems, the release of DNA from cells may not be a simple consequence of cell death but rather may require the intervention of other cell types including macrophages. Thus, in mice, administration of either apoptotic or necrotic cells produces a blood DNA response, whereas mice lacking macrophages fail to show blood DNA under the same conditions. Furthermore, the circulating DNA arising from apoptotic and necrotic cells displays a similar pattern with respect to size distribution, with both showing DNA laddering, a pattern indicating enzymatic cleavage. Since circulating DNA in the form of immune complexes can play a role in lupus pathogenesis, these findings suggest that the generation and clearance of dead cells are important events that may underlie autoimmunity in this disease and may be targeted for therapy.