C1 Esterase Inhibitor

C1 Esterase Inhibitor (C1NH) is a protein that inhibits pro-inflammatory proteins by forming an irreversible covalent bond with them. The bound proteins together with the C1NH are then cleared from the system. C1NH plays critical inhibitory roles in the complement system (C1r, C1s), the intrinsic coagulation pathway (Factor XIIa and kallikrein) and the fibrinolytic system (a system that dissolves clots once a plug forms). The absence of inhibition of these inflammatory pathways leads to increased production and release of bradykinin. Bradykinin is a molecule that promotes vascular permeability and results interstitial fluid into surrounding tissues.

HAE is a disorder where mutations in a gene (SERPING1) encoding the C1NH occurs [1]. Patients with Type I Hereditary Angioedema (HAE) produce little or no C1NH. Patients with Type II HAE produce normal levels of C1NH but the C1NH is physiologically dysfunctional. Patients supplemented with human plasma derived C1NH results in homeostasis of the inflammatory pathway, the plasma kallikrien and factor XIIa are inhibited, and the vascular permeability regulated, elevating the edema in HAE patients.

  1. National Institute of Health (NIH) Genetics Home Reference. Apr 2009. 

Applications:

  • Hereditary Angioedema