Complement C4

Quantitation of C4 is used to detect individuals with inborn deficiency of this factor or those with immunologic disease in whom hypercatabolism of complement causes reduced levels. These diseases include lupus erythematosus, serum sickness, certain glomerulonephritides, chronic active hepatitis, and others.

C4 is used only by the classical pathway, so that it is decreased only when this arm is activated. In diseases activating the alternate pathway alone, C4 levels will be normal. Total hemolytic activity (CH50), C3, and C4 are frequently decreased in a variety of conditions producing immune complexes. C4 levels are sensitive indicators of lupus disease activity. In hereditary angioedema, the lack of C1 esterase inhibitor allows unopposed lysis of C2 and C4 by C1 esterase, so C4 levels will be low. C4 deficiency has been described in association with a clinical SLE-like disease but with absence of LE cells and variable immunoglobulin or C3 deposits in the skin biopsy, and with Henoch-Schönlein purpura or glomerulonephritis. The condition is inherited as an autosomal recessive trait with close HLA linkage. Hereditary C4 deficiency has been associated with an increased incidence of pyogenic bacterial infections.