The Role of Complement in Hereditary Angioedema

Low levels of Cl inhibitor, the main inhibitor of the classic complement system, result in paroxysmal angioedema attacks that can be incapacitating or even life-threatening in affected individuals. Molecular defects in the gene for Cl inhibitor cause hereditary angioedema. In recent years, new insights in the pathways leading to angioedema due to a deficiency of Cl inhibitor have been gathered. Bradykinin, which is formed upon activation of the kallikrein-kinin system under insufficient regulation by Cl inhibitor, plays a crucial role. Whereas Cl inhibitor also occupies a central mediatory role in other plasma systems, such as the contact activation system of coagulation and the fibrinolytic plasminogen-plasmin system, a Cl inhibitor deficiency may also cause enhanced activation of these pathways. Novel therapeutic modalities for treatment and prevention of hereditary angioedema are now available, such as different forms of Cl inhibitor concentrate and novel agents that interfere in the kallikrein-kinin system. (C) 2019 Elsevier Inc. All rights reserved.