C1-INH Quick Facts
- Molecular mass: 110 000 D
- Synthesis: Liver
- Half-Life: 64h
- Plasma concentration: 0.18 – 0.22g/l 1.7 – 2.0μmol
- Normal range: 70 – 130%
Biochemistry of C1-esterase inhibitor
C1 esterase inhibitor (C1-INH, C1-Inactivator, C1-Inhibitor) protein is a normal constituent of serum which functions as a serine proteinase inhibitor of the serpin family. C1 esterase inhibitor inhibits the complement proteases C1r and C1s, as well as the proteases kallikrein, factor XIa, XIIa and plasmin of the blood clotting system.
The concentration of C1 esterase inhibitor protein is reduced to 10-30% of normal in subjects with angioedema secondary to C1 esterase inhibitor deficiency (85% of subjects with hereditary angioedema (HAE)); in 15% of subjects with HAE, the concentrations of the inhibitor protein is normal but function is markedly reduced.
As an inhibitor of the active subcomponent of the first complement factor, the C1-Inhibitor is assigned to the complement system. The contact activation is inhibited by inhibition of factors XIIa and XIa. The inhibition of fibrinolysis connected therewith is accelerated by the direct inhibition of kallikrein and plasmin by the C1-Inhibitor as well as by the elimination of the plasmin mediated activation of prourokinase.
Clinical significance of C1-esterase
In cases of C1-inhibitor deficiency (≤ 25% of normal), recurrent oedema of the skin, the gastrointestinal tract and the trachea – as a result of uncontrolled complement activation – have been observed. Hereditary oedema (HAE) is caused by a synthesis defect of the C1-inhibitor (type I) or functional insufficiency with normal protein concentrations (type II). The acquired oedema (AAE) type I is a disease of the B-cell system, such as chronic lymphatic leukaemia. Type II of an AAE is caused e.g. by an inactivation of the C1-inhibitor through autoimmune antibodies of the IgG class.
Clinical or Research use of C1-INH
- Suspected hereditary complement defect
- Acquired C1-esterase inhibitor deficiency