Advanced Diagnostic Laboratories

Methodology

Chromogenic Substrate Cleavage (DiaPharma, Technochrom®)

Turnaround Time

up to 4 weeks

Lab Department

Complement Lab

Synonyms

C1-INH Chromogenic;C1-INH Function, European test;C1-INH Function, DiaPharma;C1-INH Function, technochrom;Complement;C1-esterase inhibitor function;CEICHR

Reference Interval

By Report

Interpretive Data

The C1-inhibitor (C1-INH) was named for its role in inhibiting the enzymatic activity of C1r and C1s; thereby inhibiting activation of the classical pathway of complement. But C1-INH also has very important abilities to inhibit proteases in the fibrinolytic, clotting and kinin pathways. Specifically C1-INH inhibits the enzymatic activity of kallikrein, factor XIa, and Hageman factor (XIIa) of the coagulation and contact pathways. Failure of C1-INH to regulate these enzymes can result in life-threatening angioedema and a condition defined as Hereditary Angioedema of HAE. HAE Type I results from a missense mutation in the C1-Inhibitor gene that causes a premature stop in protein synthesis, so no secreted protein is produced. HAE Type I accounts for 85% of HAE cases and can be diagnosed by C1-INH levels. The Type II form, is a different missense mutation in the C1-Inhibitor gene, that results in a non-functional protein but normal or above normal levels of C1-INH. A third type has recently been described, HAE Type III. HAE Type III is not linked to mutations in C1-inhibitor. Instead they are finding mutations present in the Hageman factor and other targets of C1-INH. The mechanisms of this newest form of HAE are still under investigation.

Similar symptoms are manifested by Acquired Angioedema (AAE). AAE does not result from a genetic mutation but a depletion of effective C1-INH function through consumption of blocking of activity by an auto-antibody to C1-INH. In AAE-I, the associated disorders (usually lymphoproliferative malignancies) produce complement-activating factors, idiotype/anti-idiotype antibodies, or other immune complexes that destroy C1-INH function. In AAE_II a normal 105-kd C1-INH molecule is synthesized in adequate amounts but, because of an unknown event, a subpopulation of B cells secretes auto-antibodies to the C1-INH molecule.

CPT Code

86161