Advanced Diagnostic Laboratories

Collect

Serum from a plain red top is the only acceptable sample type.
Gel barrier tubes are not acceptable.

Specimen Preparation

Allow blood to clot for 20 to 60 minutes. Centrifuge to thoroughly remove cells and immediately transfer cell-free serum to a fresh tube and freeze the cell-free serum on dry ice or at -70°C.
Preferred volume: 1 mL

Pediatric Collection

Minimum volume: 250 µL serum, frozen

Unacceptable Conditions

Thawed specimen.

Storage Transport Temp

Send frozen serum Priority Overnight via FedEx and in a well insulated container on dry ice.

Stability

Frozen at -70°C: 1 year

Notes

Suggested additional testing:

If the C1-INH Function is low, a C1-INH level (Test Code: CEIQ) may aid in determining Type I versus Type II HAE.

If AAE is suspected, testing for auto-antibodies to C1-INH should be performed (Test Code: CEIAP).

Methodology

Chromogenic Substrate Cleavage (DiaPharma, Technochrom®)

Reported

up to 4 weeks

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

Interpretation

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