Complement in the immunopathogenesis of rheumatic disease

The complement system has vital protective functions as a humoral component of the innate immune system and also through interactions with the adaptive immune system; however, when inappropriately activated or regulated, complement can cause inflammation and organ damage, and such processes are involved in the pathogenesis of many inflammatory conditions, not least rheumatic diseases. Furthermore, states of complement deficiency can predispose not only to infections, but also to autoimmune disorders, including rheumatic diseases such as systemic lupus erythematosus. In this Review, the mechanisms behind the pathogenic activities of complement in rheumatic diseases are discussed. Potential approaches to therapeutic intervention that focus on regulating complement activities in these disorders are also considered.