Description
Measurements of serum complement components C3 and C4 are useful in the diagnosis and monitoring of immune complex disease e.g. SLE and some blood associated infectious diseases. Complement concentrations are acute phase proteins and may be normal, despite complement consumption, in some inflammatory and infective disorders.C3 and C4 are measured at the same time since this gives an indication of the complement pathway (classical or alternative) which is being activated and thus the cause of this activation. C3 alone is often decreased in infectious disease (septicaemia, endocarditis), C3 and C4 are often both decreased in immune complex disease, C4 alone is characteristically decreased in angioedema, immune complex diseases particularly vasculitis and in cryoglobulinaemia and cold agglutinin disease.
Measurement of serum complement is useful in the monitoring of specific immune complex diseases e.g SLE and infectious diseases post streptococcal disease, subacute bacterial endocarditis. Consumption of one or both components may also be useful prognostically e.g nephritis in lupus.
Though genetic deficiencies of C3 are exceedingly rare, deficiencies in other components which are more common (though still very rare) can result in low C3. Genetic deficiencies in C4 are rarely detected. C1 inhibitor deficiencies are often detected by investigation of unexpected low C4 levels.
Indication
Investigation of renal/joint/connective tissue disorders and their symptoms -glomerulonephritis, vasculitis. Investigation of immunodeficency associated with recurrent infections.
Interpretation
The normal adult range of C4 is 20-50mg/dl. Values up to twice this upper limit are found in acute phase. Values <1mg/dl can be found in active immune complex disease, cryoglobulinaemia or C1-inhibitor deficiency. Low levels of C4 strongly suggest immune complex disease. They are found most commonly in cases of active SLE, rheumatoid vasculitis (but not uncomplicated rheumatoid arthritis where C4 levels are usually normal).Very low levels are found in association with normal C3 levels in acquired or hereditary C1-inhibitor deficiency (vide infra).
In some long standing SLE patients C4 levels remain low. This does not necessarily denote active disease but more likely genetic C4 deficiency and/or lack of synthesis. However a sudden fall in levels in any individual does usually indicate exacerbation of disease activity. Serial determinations are always a better guide to disease activity.
The normal adult range for C3 is 90-180mg/dl. Values up to twice this upper limit are found in acute phase. Values <1mg/dl can be found in active immune complex disease, septicaemia, bacteraemia, post streptococcal glomerulonephritis or diseases associated with nephritic factor. Low levels of C3 associated with low levels of C4 demonstrate classical pathway activation and strongly suggest immune complex disease. They are found most commonly in cases of active SLE. Low levels of C3 associated with normal levels of C4 demonstrate alternative pathway activation suggestive of infectious disease or nephritic factor activity.
Although in some long standing SLE patients C3 levels remain low, which does not necessarily denote active disease, a sudden fall in levels does usually indicate exacerbation of disease activity and a risk of renal damage.
Sample
Serum Separator Tube (SST)
Assay details
Nephelometry
Restrictions
Increased levels of lipids (lipaemia), haemoglobin (haemiolysis), or the presence of icterus in the assay sample may affect the assay result.
Reference range
C3: 0.75 – 1.65g/L
C4: 0.20 – 0.65g/L
Assay range notes
C3: range 0-4.00g/L
C4: 0-3.00g/L
Turnaround time
1 – 2 days
Analysing laboratory
Immunology The James Cook University Hospital