C1inhibitor

C1 esterase inhibitor, commonly abbreviated C1-INH, is a serine protease inhibitor (serpin) that regulates several proteolytic cascades in humans. It is primarily produced by the liver and circulates in the plasma. The SERPING1 gene encodes C1-INH, located on chromosome 11. In addition to the classical complement pathway, C1-INH also inhibits components of the contact system, including plasma kallikrein and factor XIIa, helping to control bradykinin production and vascular permeability.

Functionally, C1-INH limits activation of the C1 complex (C1r and C1s) in the classical complement pathway and suppresses the kallikrein–kinin system. By doing so, it prevents excessive generation of bradykinin, a potent vasodilator. Deficiency or dysfunction of C1-INH disrupts these regulatory pathways, leading to episodes of swelling (angioedema) without urticaria.

Clinically, C1-INH deficiency causes hereditary angioedema (HAE). Type I HAE features low circulating levels of C1-INH, while Type II HAE involves normal or elevated C1-INH levels that are dysfunctional. Acquired C1-INH deficiency can occur with autoimmune or lymphoproliferative diseases. Symptoms include recurrent facial, oral, gastrointestinal, or genital swelling, and life-threatening laryngeal edema. Triggers may include trauma, infections, surgery, or hormonal changes.

Diagnosis relies on complement testing (reduced C4 levels during attacks, reduced C1-INH function, and/or reduced antigen or functional levels) and genetic testing for SERPING1 mutations. Treatments for attacks include C1-INH concentrates (plasma-derived or recombinant), kallikrein inhibitors, and bradykinin B2-receptor antagonists. Prophylaxis may involve regular C1-INH dosing or other agents; in some cases androgens or tranexamic acid are used.