Complement System
A cascade of approximately 30 proteins in the innate immune system that destroys pathogens, promotes inflammation, and clears damaged cells. Dysregulated complement activation contributes to autoimmune diseases. Zilucoplan inhibits complement C5 for the treatment of generalised myasthenia gravis.
Technical Context
Complement activation pathways: classical (antibody-antigen complexes activate C1 → C4 → C2 → C3 convertase C4b2a), lectin (mannose-binding lectin binds pathogen surfaces → MASP-1/2 activate C4 → C2 → same C3 convertase), and alternative (spontaneous C3 hydrolysis — tick-over — amplified on foreign surfaces lacking complement regulators → Factor B/D → C3 convertase C3bBb). All three converge on C3 cleavage → C3a (anaphylatoxin — inflammation) + C3b (opsonin — coating pathogens for phagocytosis, also feeds into C5 convertase). C5 convertase cleaves C5 → C5a (potent anaphylatoxin and chemotactic factor) + C5b → C5b-6-7-8-9 = membrane attack complex (MAC — forming pores in target membranes). Zilucoplan inhibits C5 cleavage, preventing both C5a-mediated inflammation and MAC formation at the neuromuscular junction in myasthenia gravis.