C1-inhibitor is a protease inhibitor which controls activation of the complement pathway by inhibiting activated C1r and C1s. It also inhibits enzymes in the blood clotting, clot lysis and kinin generating pathway. Genetic deficiency of C1 inhibitor (antigenic or functional) is transmitted as an autosomal dominant disorder resulting in Hereditary Angioedema – a disease characterised by painless swellings on limbs or trunk or by recurrent abdominal pain. Many deficient individuals show no family history. Most patients have low levels of C1-inhibitor though some have normal levels of non-functional inhibitor; thus Hereditary C1-inhibitor deficiency can be antigenic (Hereditary Type 1) or functional (Hereditary Type 2).
There is also an acquired form of C1 inhibitor deficiency usually associated with autoantibodies against C1-inhibitor which may occur with B cell lymphoma. Genetic deficiencies of C1 inhibitor can be first detected at any age, when symptoms appear. The rarer acquired form is usually detected in middle or old age. The range of symptoms in each form of the disease is the same.
Samples collected during or shortly after an an acute attack of angioedema are almost always characterised by a low C4 level (and normal C3). In samples with suggested hereditary angioedema and low C4 but normal C1-inhibitor levels, a functional assay will be carried out automatically or second sample requested.
Investigation of angioedema oedema and/or recurrent abdominal pain or other unexplained gut problems.
Low C1-inhibitor level determined by nephelometry is almost always caused by hereditary or acquired deficiency as described. Complement activation by inflammatory or infectious diseases does not lower C1-inhibitor. Note that not all C1-inhibitor patients are symptomatic and some can be identified by the laboratory in samples found to have very low C4 levels with no apparent cause. Functional deficiencies account for about 15% of cases. The functional assays are somewhat problematic and need to be interpreted with care. The laboratory will advise.
Serum Separator Tube (SST)
Nephelometry; C3 and C4 are also determined at the same time.
Increased levels of lipids (lipaemia), haemoglobin (haemiolysis), or the prescence of icterus in the assay sample may affect the assay result. The laboratory must be contacted if functional C1 – inhibitor assay is required.
Antigenic assay: 0.15-0.35g/L
Functional assay: 70 – 130 U/L
Assay range notes
Antigenic assay: 0. – 0.50 g/L. Functional C1inhibitor assays are related to normal samples (100U/L) tested on the same day.
3 – 5 days (antigenic), 28 days (functional assay)
Immunology The James Cook University Hospital
Functional assay is sent to Sheffield PRU