The complement system in pediatric systemic lupus erythematosus, atypical hemolytic uremic syndrome, and...

This review summarizes the recent advances in complement biology and the evolving understanding of these contributions to the pathophysiology and treatment of predominantly pediatric disease syndromes.

Identification of lupus patients with complete deficiencies of one of the plasma complement proteins enabled the field to move beyond the notion of complement as a laboratory curiosity. Clinical investigation of the manifestations observed in deficient patients has further defined the biology of the system in normal individuals. Definition of the assembly of the C3 convertases, particularly that of the alternative pathway and its regulation, has led to the appreciation that the complement system includes membrane inhibitors that are every bit as important as those in plasma. The exploration of disease states in which significant complement deposition occurs has moved the field away from consideration of this finding as a bystander effect. Dissection of these syndromes has led to the unanticipated finding of a central role for function-altering mutations in the complement proteins that form or regulate the alternative pathway C3 convertase and has opened the door to new therapeutic approaches. The disease states discussed in the review - pediatric systemic lupus erythematosus, atypical hemolytic uremic syndrome, and the complocentric membranoglomerulopathies - illustrate this evolutionary history of complement biology.

This review emphasizes that both the lack of classical pathway complement activation and excessive activation of the alternative pathway contribute to distinct disease pathogenesis, and emphasizes the critical importance of homeostatic regulation, in both plasma and in tissues, of the system as a whole.