Complement C3 and C4

C3 and C4 are acute phase proteins with central roles in the innate immune complement enzyme cascade system. Complement activation results in opsonisation and lysis of pathogens.

Low C3 and C4 may be found in immune complex disease (SLE, HUVS, cryoglobulinaemia) or sepsis and indicates classical pathway activation. Low C4 in isolation can also be seen in immune complex diseases but is also found in AIHA and C1 inhibitor deficiency. Incidental findings of low C4 with normal C3 in a healthy patient may be due to low C4 copy number, found in 5% of the population. Complement C3/C4 are considered to be markers of disease activity in SLE and are measured as part of routine follow up in these patients.

Low C3 with normal C4 indicates alternative pathway activation and may be seen in sepsis, post-infectious glomerulonephritis and disorders resulting from abnormal regulation of the alternative pathway (e.g. C3 nephritic factors, factor H/I deficiency). A rare inborn error of immunity with susceptibility to encapsulated bacteria and an SLE-like disease can be caused by mutations in C3.

This assay is performed by turbidimetry.

Immune complex disease
Renal disease
Joint disease
Vasculitis