C1 ESTERASE INHIBITOR (C1 INHIBITOR)

CLINICAL UTILITY:

Measuring the functional effect of the C1 esterase inhibitor protein is important in the diagnosis of Hereditary Angioedema (HAE), a disease in which the protein is either decreased, absent, or inactive. In normal individuals, the protein blocks the enzymatic activities of the C1 esterases, C1r and C1s, inhibiting complement activation. The diagnosis of angioedema with depressed C1 esterase inhibitor (C1 inhibitor) should be suspected in patients with severe or recurrent angioedema, especially when the angioedema involves the oropharynx and leads to airway obstruction, or involves the abdominal wall and leads to abdominal pain or intestinal obstruction. The condition can be confirmed in the laboratory by finding depressed levels of C1 esterase inhibitor. In HAE, the C1 inhibitor protein level (measured antigenically) is less than normal in 85% of cases. In about 15% of patients, the protein level is normal but the protein is dysfunctional. Measurement of both C1 esterase inhibitor protein level and functional activity is useful.

In addition to HAE (due to congenital deficiency of C1 inhibitor), deficiency of C1 inhibitor may develop in patients with lymphoproliferative malignancies or immune complex disorders. Since the acquired form of the condition is usually associated with immune complex activation of the early complement components, C1q levels are low in acquired C1 inhibitor deficiency, but normal in HAE. In both acquired and HAE with C1 inhibitor deficiency, the C4 level is low, especially during attacks of angioedema.

METHOD DESCRIPTION:

The functional assay is performed by radial immunodiffusion (RID) inhibition, assaying the C1r level in the patient’s serum before and after C1 is activated by model immune complexes. If C1 esterase inhibitor is present in sufficient quantity, C1r will be blocked, and will not form a precipitin ring with the antibody in the gel. If C1 esterase inhibitor is insufficient, C1r will diffuse into the gel and form a precipitin ring as it complexes with the antibody.

The quantitative protein level is assayed by RID. The routine test for C1 esterase inhibitor includes both the functional assay and the quantitative protein level.

REFERENCE RANGE:

Functional assay: > 68% of normal function.
C1 esterase inhibitor protein: 10-19 mg/dl

SPECIMEN REQUIREMENTS:

Functional assay: 1.0 ml serum (freeze within two hours and send on dry ice.)
C1 esterase inhibitor protein: 0.5 ml serum (send on dry ice.)