C1-Esterase Inhibitor: Biological Activities and Therapeutic Applications

Human C1-esterase inhibitor (C1-INH) is a unique anti-inflammatory multifunctional plasma protein best known for its key role in regulation of the classical complement pathway, contact activation system and intrinsic pathway of coagulation. By sequence homology and mechanism of protease inhibition it belongs to the serine proteinase inhibitor (serpin) superfamily. However, in addition to its inhibitory capacities for several proteases, it also exhibits a broad spectrum of non-inhibitory biological activities. C1-INH plays a key role in the regulation of vascular permeability, best demonstrated in hereditary angioedema (HAE) which is triggered by the deficiency of functional C1-INH in plasma. Since 1963, when the link between HAE and C1-INH was first identified, considerable progress has been made in the investigation of C1-INH structure and biological activities, understanding its therapeutic potential, and in the research and development of C1-INH-based therapies for the treatment of HAE and several other clinical conditions. However, augmentation therapy with C1-INH concentrates for patients with HAE is currently the only approved therapeutic application of C1-INH. This manuscript provides an overview of the structure and functions of human C1-INH, its role in HAE, summarizes published data available for recently approved C1-INH therapeutic products, and considers possible use of C1-INH for other applications. *Corresponding author: Elena Karnaukhova, PhD, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, National Institutes of Health Building 29, Bethesda, Maryland 20892, USA, Tel: 301-402-4635; Fax: 301-402-2780; E-mail: [email protected] Received February 06, 2013; Accepted May 13, 2013; Published May 15, 2013 Citation: Karnaukhova E (2013) C1-Esterase Inhibitor: Biological Activities and Therapeutic Applications. J Hematol Thromb Dis 1: 113. doi: 10.4172/23298790.1000113 Copyright: © 2013 Karnaukhova E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.