C3, C4 AND FACTOR B (C3 PROACTIVATOR)

CLINICAL UTILITY:

Serum levels of C3, C4 and Factor B (C3 Proactivator) are usually monitored to detect complement activation in disease processes. If activation is caused by immune complex-mediated disorders, the classical pathway wil be utilized; serum levels of C3 and C4 will be lowered, but Factor B levels will be normal. Alternative pathway activation results in lower serum levels of C3 and Factor B, but normal levels of C4. Therefore, whenever it is important to determine which pathway is involved, the levels of C4 and/or Factor B are helpful, since C3 is lowered in both pathways.

Classical pathway activation occurs in early stages of SLE and in other immune complex related diseases. If the activation is not severe, only C4 will be depleted, leaving C3 at a normal level. In more active stages of SLE, both C4 and C3 are usually low. In Hereditary Angioedema (HAE), C4 levels are almost always very low, and in addition, C1 esterase inhibitor is either low or functionally inactive. In HAE the level of C1q protein (C1) is normal. (See test descriptions of C1 Esterase Inhibitor and C1). In acquired angioedema with C1 esterase inhibitor deficiency, associated with lymphoproliferative malignancies and immune complex diseases, C4 and C1q protein are both low. In a small percentage of cases, patients with angioedema and urticaria have immune complex-induced complement activation. Serum levels of C4, C3 and CH50 may all be low, with high immune complex levels.

Alternative pathway activators include non-immunologic agents such as bacterial endotoxins and surface polysaccharides, yeast cell walls and aggregates of IgA. In addition, the alternative pathway of complement is activated in some forms of idiopathic membranoproliferative glomerulonephritis (“dense deposit disease”). Therefore, consumption of C3 and Factor B is associated with infectious processes of glomerulonephritis.

Since complement levels change during the course of a disease, it is important to correlate the test results with the clinical assessment. Complement proteins are also acute phase reactants; therefore, elevated serum levels occur with inflammation not associated with complement activation, and reflect disease activity.

METHOD DESCRIPTION:

C3 and C4: Serum levels of C3 and C4 are determined antigenically by a turbidimetric procedure.
Factor B: SIngle radial immunodiffusion (RID) is the method used to quantitate the serum level of Factor B.

REFERENCE RANGE:

C3: 70-170 mg/dl
C4: 10-40 mg/dl
Factor B: 9-31 mg/dl

SPECIMEN REQUIREMENTS:

C3 and C4: 0.3 ml serum. (Both tests can be performed on same aliquot.) Send on dry ice, since complement levels may change unless sample is kept frozen at -70°C.
Factor B: 0.5 ml serum. Send on dry ice. (See above.)