Complement as a Therapeutic Target in Systemic Autoimmune Diseases

Abstract

The complement system (CS) includes more than 50 proteins and its main function is to recognize and protect against foreign or damaged molecular components. Other homeostatic functions of CS are the elimination of apoptotic debris, neurological development, and the control of adaptive immune responses. Pathological activation plays prominent roles in the pathogenesis of most autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, dermatomyositis, and ANCA-associated vasculitis. In this review, we will review the main rheumatologic autoimmune processes in which complement plays a pathogenic role and its potential relevance as a therapeutic target.

Keywords: complement system; pathogenesis; rheumatic autoimmune diseases; therapeutic blockade.

Figure 1

Complement system. There are three activation pathways in the complement system: classical, lectin, and alternative. All three pathways lead to the formation of C3 and C5 convertases, which rapidly amplify the complement response. In addition to the processes described above, several complement regulatory proteins are able to inhibit complement by inactivation of C3 and C5, and C3 and C5 convertases, or by preventing successful formation of the membrane attack complex. DAF: decay-accelerating factor or CD55; FB: factor B; FD: factor D; FH: factor H; FI: factor I; MASPs: MASP: MBL-associated serine proteases; MCP: membrane cofactor protein or CD46; MIRL: membrane inhibitor of reactive lysis or CD59; P: properdin.