Figure 1.

The complement system has both pathogenic and protective roles in systemic lupus erythematosus. Complement proteins have multiple functions that affect lupus, both positively and negatively. The classical pathway may help facilitate the removal of apoptotic and damaged cells as well as immune complexes, reducing the risk of developing autoimmunity to nuclear components. C1q may also directly reduce CD8 T cell activation, thereby attenuating downstream immunity and autoantibody generation. Once activated, however, the complement system can promote tissue injury and disease severity. The complement system can directly cause cytotoxic injury in tissues, and also increases inflammation by attracting leukocytes and inducing interferon production by dendritic cells. Complement fragments may also increase T cell and B cell responsiveness, increasing the response to autoantigens.