Factor I

Factor I (FI) is a serine protease with narrow specificity restricted to activated complement components C3b and C4b. Supported by appropriate cofactors such as factor H or C4b-binding protein, FI cleaves peptide bonds in C3b/C4b after arginyl residues. By doing so it inhibits further propagation of the complement cascade thus contributing to protection from misguided or excessive complement attack on own cells and tissues. Furthermore, inactivated fragments of C3b bind to specific receptors on immune cells and influence their function such as phagocytosis. Production and secretion of FI into bloodstream is mainly supported by liver but extrahepatic sources were also identified, such as keratinocytes, fibroblasts, monocytes and endothelial cells. Mutations/polymorphism in FI may diminish its secretion or cause loss of function. When leading to complete deficiency, alterations in FI markedly distort the balance between complement activation and inhibition. The outcome is increased rate of bacterial infections and glomerulonephritis. Partial deficiency of FI predisposes to atypical haemolytic uraemic syndrome or age-related macular degeneration.