Complement C4

The Complement C4 test (C4 complement; fourth complement component) is used to quantify C4 to identify congenital deficiency and to recognize decreased levels from accelerated breakdown or consumption in immunologic disease. It supports diagnosis and longitudinal monitoring of immune complex–mediated disorders, including systemic lupus erythematosus, serum sickness, certain glomerulonephritides, and chronic active hepatitis. Additional applications include assessing immune status in infectious diseases and evaluating predisposition to systemic lupus erythematosus. C4 measurement is frequently interpreted alongside C3 to appraise classical pathway integrity.

The complement system comprises plasma proteins that enhance host defense through opsonization, lytic injury to cells, and modulation of inflammation. Activation occurs by distinct routes; C4 participates in the classical pathway, which is triggered by antigen–antibody complexes. C4 is synthesized predominantly in the liver and contributes to opsonization, neutralization of viruses, and increased vascular permeability. During classical pathway activation with immune complex formation, C4 is consumed and can bind to immune complexes, leading to reduced circulating concentrations. Congenital C4 deficiency is associated with heightened susceptibility to infections and a predisposition to systemic lupus erythematosus. For assessment of complement pathway integrity, C4 is commonly measured in concert with C3.