Special Precautions/Comments:

Interference: Grossly lipaemic, icteric or haemolysed samples are unsuitable for nephelometric assay.

Interpretation: C1 inhibitor quantitation and functional activity should be intepretated in conjunction for diagnosis of HAE/ AAE. C1 inhibitor functional activity may be reduced in cases of transit delay. Under these circumstances concentrations down to 40% may be considered as ‘normal’ if associated with a C4 within the reference range. Reduced C1 inhibitor function may also be caused by the use of exogeneous oestrogens, including oral contraceptive agents. C1 inhibitor is an acute-phase protein and can be increased in inflammatory processes as well as the administration of exogenous androgen and related steroids. Intepretation should consider family and clinical/ past medical history.

Additional Information:

Indication: Investigation and monitoring of Hereditary/Acquired Angioedema

References: PRU handbook of Clinical Immunochemistry. 9th Edition. 2007. [Ref 1] Gompels MM, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005. 139(3):379-394. [Ref 2] Markovic SN, et al. Acquired C1 esterase inhibitor deficiency. Ann Intern Med. 2000. 132(2):144-150. [Ref 3] Bork, et al. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000. 356:213-217. [Ref 4]

Background Information: C1 esterase inhibitor is an alpha-2 globulin serpin inhibitor. In its composite role as inhibitor of the recognition unit of the classical complement pathway, the coagulation and the kinin systems, C1 inhibitor is a major regulatory protein in the inflammatory response [1]. Hereditary angiodema (HAE) is an autosomal dominant condition, caused by deficiency of C1 esterase inhibitor. It is the commonest of the inherited complement component deficiencies with an incidence is in the order of 1:50,000 [2]. Two main forms of the inherited deficiency exist. In HAE type 1 both quantitative and functional C1 inhibitor levels are decreased as a results of ineffective protein secretion due to gene mutations. In HAE type 2, which accounts for 15% of cases, the C1 inhibitor quantitation can be either normal or elevated by the antigenic assay but have absent functional activity due to the secretion of a non-functional protein [1,2]. Acquired C1 inhibitor deficiency is a rare form, presenting for the first time in adult life. All reported cases have been secondary to lymphoma or myeloma, and full evaluation of the serum and urine immunoglobulins is indicated in these cases. In both the hereditary and aquired forms the C4 level is usually low but the C3 is normal [3]. More recently a third type of hereditary angioedema has been described. This oestrogen-dependent condition has mainly been observed in women but does not result in abnormally low functional or quantitative C1 inhibitor levels [4].

See Also: C3; C4

Telephone Gateshead Lab: 0191.4456499 Option 4, Option 1