C1s, C1r, Plasma kallikrein, and Factor XIIa (Group of Serine Proteases)

C1s and C1r are serine proteases that are part of the C1 complex, initiating the classical pathway of complement activation; C1-INH is the natural inhibitor that blocks excess activation to prevent inflammation and vascular leak[5][3]. Plasma kallikrein and its precursor (prehuman kallikrein) are enzymes that trigger the release of bradykinin from kininogen and reciprocally activate Factor XII; bradykinin is critical for vasodilation and increased permeability[1][6]. Coagulation factor XIIa (Hageman factor, FXIIa) is responsible for activating factor XI and initiating the intrinsic pathway of blood coagulation[1][2][8]. Together, these enzymes play integral roles in the regulation of blood coagulation, complement activation, inflammation, and edema; their dysregulation is linked to hereditary angioedema and other vascular or inflammatory disorders[1][3][5][9].

Other names

Complement C1sC1 esteraseC1s subcomponentComplement C1rC1r subcomponentKallikreinKLKB1Fletcher factorHageman factorActivated Hageman factorFXIIa

Direct inhibition of serine protease activity (e.g., inhibitors block the active site of C1s, C1r, plasma kallikrein, or Factor XIIa) - Restoration of C1-INH levels to suppress activation of all four proteases - Receptor antagonism for bradykinin (downstream effect)