C1INH

C1 esterase inhibitor (C1INH) is a serine protease inhibitor of the SERPIN family that regulates several proteolytic cascades in the immune and inflammatory systems. It mainly inhibits C1r and C1s of the classical complement pathway, as well as proteases of the contact system, including factor XIIa and plasma kallikrein, and to a lesser extent plasmin and factor XIa. By constraining these proteases, C1INH limits generation of bradykinin and vascular permeability during inflammatory responses.

Most C1INH is produced by the liver and circulates in blood plasma as a glycoprotein of about 68–78 kDa, depending on glycosylation.

Deficiency or dysfunction of C1INH leads to hereditary angioedema (HAE). HAE types include Type I (reduced C1INH levels) and Type II (normal or elevated levels with dysfunctional protein); a rare Type III is associated with mutations in the F12 gene. Acquired angioedema can occur due to consumption or autoantibodies against C1INH and is often linked to lymphoproliferative or autoimmune conditions. The condition is characterized by episodic, sometimes life-threatening swelling, most commonly affecting the skin, abdomen, and airway.

Clinical management focuses on preventing or treating swelling episodes. Acute attacks are treated with C1INH concentrates (plasma-derived or recombinant) or with agents that inhibit kallikrein or block bradykinin receptors in various settings. Long-term prophylaxis may include regular C1INH replacement or newer therapies such as plas mak kallikrein inhibitors or monoclonal antibodies targeting kallikrein. Ongoing monitoring of C1INH levels and function is important for diagnosis and management, including during pregnancy or before procedures.