Hereditary angioedema (HAE): Deficiency of C1 esterase inhibitor is the most frequent of the inherited complement component deficiencies. The incidence is not well defined but is in the order of 1:50,000 in the UK Caucasian population. The condition is inherited as an autosomal dominant trait. Several members of a family are usually affected. The commonest symptoms are episodes of painless swellings on the limbs or trunk which subside in 24-48 hours. Recurrent abdominal pain (due to mesenteric oedema) or respiratory obstruction (due to laryngeal oedema), which can be fatal, may also form part of the clinical picture. The clinical condition was first described by Osler in 1888 and may be referred to as Osler’s Disease.
The angioedema is characterised by recurrent, circumscribed, non pruritic episodes of subepithelial oedema of the skin or submucosal oedema of the gastrointestinal and respiratory tract. In the skin the oedema may be preceded by a faint macular or serpiginous erythema but not by urticaria. The anatomical origin of the tissue oedema has been demonstrated as a leakage from the postcapillary venules.
The mortality, which may be considerable, is inherent in the predeliction for certain affected individuals to develope laryngeal or glottic oedema with acute airway obstruction.
In view of the autosomal dominant inheritance of this condition, and its potential morbidity and mortality, full family studies are essential in all cases where the diagnosis is proven. The investigation can, at the first instance, be restricted to quantitation of C3 and C4 levels. Antigenic and functional assay of C1 INH can be reserved for those family members who have been shown to have subnormal C4 concentrations in the light of normal concentrations of C3.
Acquired C1 inhibitor deficiency: There is a rare acquired form of C1 inhibitor deficiency presenting for the first time in adult life. Most reported cases have been secondary to lymphoma or myeloma, and full evaluation of the serum and urine immunoglobulins is indicated in these cases. This is a consumptive, rather than a synthetic, defect and is associated with low concentrations for complement C1q.
Rare autoantibodies to C1q and to C1-INH have been described with the same symptomatology.
Sample requirement: 2 mL serum.
Normal adult concentrations 0.15 – 0.35 g/L
Normal concentrations for the functional assay are in the range 75 – 125% of a normal reference plasma.
Lower concentrations are seen in serum and when the sample has been transported at ambient temperature. Under these circumstances concentrations down to 40% may be considered as ‘normal’ if associated with a C4 within the reference range.
Serum levels are increased by the administration of exogenous androgen and related steroids, whilst they are decreased by exogenous oestrogens, including oral contraceptive agents.
Centres offering this assay:
London St George’s Hospital PRU Diagnostic Service
Sheffield Northern General’s PRU Diagnostic Service