C1 Inhibitor Autoantibodies

Autoantibodies to C1 inhibitor (C1-INH) bind to epitopes on the reactive center of the C1-INH molecule. As a consequence of this binding, C1-INH is converted into an inactive substrate that can be cleaved by proteases. C1-INH is a serine protease inhibitor that plays a role in the complement, contact, fibrinolytic, and coagulation cascades. Autoantibodies to C1-INH cause acquired C1-INH deficiency, activation of the classical complement pathway, and defective control of the contact-kinin system. This eventually leads to recurrent bradykinin release with increased vascular permeability and symptoms of angioedema involving subcutaneous tissue, gastrointestinal mucosa, and the upper respiratory tract. Autoantibodies inactivate C1-INH protein and may dramatically reduce efficacy of replacement therapy with plasma derived C1 inhibitor. Autoantibodies to C1-INH have also been described in absence of angioedema symptoms. They have been found in patients with systemic lupus erythematosus (SLE), with lupus-like syndrome and anticardiolipin antibodies and in a patient with primary antiphospholipid syndrome: their effect on C1-INH function in these conditions is only partially defined. © 2014 Elsevier B.V. All rights reserved.