Clinical Summary

The complement system is an integral part of the antigen-nonspecific immune defense. It can be activated via two reaction pathways, the classical pathway which is triggered primarily by cellbound immune complexes, and the alternative pathway which is activated primarily by foreign bodies such as microorganisms. The complement component C3 is a key protein in both reaction pathways whereas C4 belongs to the classical pathway of complement activation. Complement activation is associated with consumption of components C3 or C4 so that a reduction in their concentrations can allow diagnostic conclusions to be reached. Diminished serum concentrations of C3 and C4 are observed primarily in active systemic lupus erythematosus (SLE), in forms of membrane proliferative glomerulonephritis and in immune complex diseases (serum sickness). In the case of SLE the serum concentrations of the complement factors reflect the activity of the disease. Diminished C3 values occur in acute glomerulonephritis and in membrane proliferative glomerulonephritis whereas isolated diminished levels of C4 can occur in hereditary angioedema (HAE) and in cases of autoimmune hemolytic anemia. Both complement components react as acute-phase proteins and may therefore show elevated serum concentrations in patients with inflammatory diseases. Hereditary deficiency states of both complement factors have been reported.