Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation.

ABSTRACT: Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. However, several reports suggest that activation of C5 is not always completely suppressed in patients even under excess of eculizumab over C5, indicating that residual C5 activity may derogate the drug's therapeutic benefit under certain conditions. By using eculizumab and the tick-derived C5 inhibitor coversin, we determined conditions ex vivo in which C5 inhibition is incomplete. The degree of such residual lytic activity depended on the strength of the complement activator and the resulting surface density of the complement activation product C3b, which autoamplifies via the alternative path

SUBMITTER: Harder MJ 

PROVIDER: S-EPMC5324716 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature