Fig. 1.

Complement activation and the mechanism of action of Eculizumab. The AP constantly undergoes ‘tick-over’ but can also be primed by the CP and LP pathways. The C3b that is formed interacts with factor B (B), which is then cleaved by factor D to form the AP C3 convertase (C3bBb). This enzyme complex is attached to the target covalently via C3b while Bb is the catalytic serine protease subunit. Because C3 is the substrate for this convertase, a powerful feedback loop is created. Unchecked, this will lead to activation of the terminal complement pathway with generation of the effector molecules; the anaphylatoxin C5a and the membrane attack complex (MAC). Eculizumab binds C5 and prevents its entry into the C5 convertase (C3bBbC3b), thus precluding cleavage into the effector molecules, C5a and C5b and ultimately the MAC.