Complement component C8 (C8)

Complement component C8 is a 150-kDa heterotrimeric glycoprotein that serves as a pivotal component of the terminal complement pathway. It consists of three non-identical subunits: alpha (C8A), beta (C8B), and gamma (C8G), with the alpha and beta subunits belonging to the membrane attack complex/perforin (MACPF) family and the gamma subunit being a member of the lipocalin family. C8's primary biological function is to initiate the penetration of the target cell membrane and coordinate the polymerization of C9 to form the membrane attack complex (MAC), which leads to cell lysis. Dysregulation of C8 and the MAC is associated with several inflammatory and autoimmune conditions, such as paroxysmal nocturnal hemoglobinuria (PNH) and age-related macular degeneration (AMD), while its deficiency leads to increased susceptibility to Neisseria infections. Although no drugs specifically targeting C8 are currently approved, the terminal pathway is therapeutically modulated by C5 inhibitors like eculizumab and ravulizumab, which prevent the formation of the MAC. Research into specific C8 inhibitors is ongoing, as they may offer a more targeted approach with a potentially lower risk of infection by preserving upstream complement functions.

Other names

Complement 8Complement Component 8C8A (alpha subunit)C8B (beta subunit)C8G (gamma subunit)

Inhibition of membrane attack complex (MAC) assembly and prevention of pathological cell lysis by blocking the terminal complement pathway.