Complement alternative pathway proteins (AP)

The complement alternative pathway (AP) is a vital component of the innate immune system that provides continuous surveillance and rapid response to pathogens through a 'tick-over' activation mechanism. Unlike the classical and lectin pathways, the AP is constitutively active at low levels and does not require specific antibody recognition for initiation. It relies on a group of proteins, most notably Complement Factor B, Complement Factor D, and Properdin, which interact with C3b to form the C3 convertase (C3bBb) enzyme complex. This complex acts as a powerful amplification loop, significantly increasing the production of C3b and downstream effectors like the membrane attack complex. Dysregulation or overactivation of these proteins is a primary driver in several rare hematological and renal diseases, such as paroxysmal nocturnal hemoglobinuria (PNH) and C3 glomerulopathy. Therapeutic strategies focus on inhibiting specific AP enzymes like Factor B or Factor D to selectively block this amplification loop while preserving the protective functions of the classical pathway. Recent drug approvals, such as Iptacopan and Danicopan, demonstrate the clinical utility of targeting these specific alternative pathway components.

Other names

Alternative pathway of complementComplement Factor BComplement Factor DProperdinC3bBb convertase componentsComplement Factor HComplement Factor I

Inhibition of specific alternative pathway enzymes, primarily Factor B or Factor D, to prevent the formation and stabilization of the C3 convertase (C3bBb). This action blocks the amplification loop of the complement system, reducing C3 consumption and the subsequent generation of proinflammatory anaphylatoxins and the membrane attack complex.