Complement factor I (CFI) (CFI)

Complement factor I (CFI) is a crucial soluble serine protease that serves as a primary regulator of the alternative, classical, and lectin complement pathways (UniProt P05156). It functions by cleaving the active complement components C3b and C4b into their inactive fragments, iC3b and iC4b, in the presence of essential cofactors such as Factor H, C4b-binding protein, or Membrane Cofactor Protein (CD46) (Lachmann, 2009). In the kidney, podocyte-expressed CFI and other regulators are vital for maintaining the integrity of the glomerular filtration barrier against autologous complement-mediated damage (Kavanagh et al., 2008). Genetic mutations or low levels of CFI are strongly associated with diseases characterized by complement overactivation, including age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and C3 glomerulopathy (PubMed 28606301). Therapeutic strategies currently under investigation focus on restoring or enhancing CFI activity through gene therapy or recombinant protein replacement to mitigate tissue damage caused by uncontrolled complement amplification. For instance, GT005 is an investigational AAV-based gene therapy designed to increase CFI production in the eye for AMD patients (ClinicalTrials.gov NCT03846193).

Other names

Factor IC3b/C4b inactivatorC3BINAFIKAFIF

CFI acts as a serine protease that cleaves the alpha chains of C3b and C4b into inactive forms (iC3b and iC4b), thereby preventing the formation and activity of C3 and C5 convertases and limiting the amplification of the complement cascade (Lachmann, 2009).