complement C4 in serum

Reference interval

Table

age	MEAN mg/dL	RANGE mg/dL
Adult	28	15-45
CORD BLOOD	13	6.6-23
1 month	14	7.0-25
2 months	15	7.4-28
3 months	16	8.7-27
4 months	19	8.3-38
5 months	18	7.1-36
6 months	21	8.6-42
7-9 months	20	9.5-37
10-12 months	22	12-39
1 year	23	12-40
2 years	19	9.2-34
3 years	20	9.7-36
4-5 years	21	13-32
6-8 years	20	12-32
9-10 years	22	10-40

Principle

The Beckman Array Protein System, in conjunction with the C4 Reagent Test Kit, is intended for in vitro diagnostic quantitation of C4 of biological fluids by rate nephelometry.

The complement proteins are a group of at least 20 immunologically distinct components in blood & tissue fluids. They are able to interact sequentially with antigen-antibody complexes, with each other, & with cell membranes in a complex but adaptable way to destroy viruses & bacteria &, pathologically, even the host's own cells. Complement proteins are synthesized by the liver & are normally present in the blood as functionally inactive molecules. A sequence of interactions can be activated by antigen-antibody complexes through the 'alternative' or non-classical pathway from C1 to C5, or even by non-antibody initiating factors through the 'alternative' or non-classical pathway from C3 to C5. Either path leads to the final membrane attack sequence (C5 to C9 & lysis).

The whole process is controlled by the very short life of many of the intermediates & by the presence of specific inhibitor proteins which are an integral part of the system.

Clinical significance

Abnormal serum levels of complement proteins may be due to either inherited or acquired diseases.

Inherited angioedema is an autosomal dominant disease that results from a deficiency of C1 esterase inhibitor. It is characterized by attacks of subcutaneous, bronchial, & gastrointestinal edema. Spontaneous activation of uninhibited C1 leads to consumption of C1 & C2, but not of C3 or later components. A peptide breakdown product of C2 is responsible for the vascular permeability that leads to edema. Laboratory findings include low levels of C4 & C1 esterase inhibitor,but normal levels of C3. In about 15% of cases, C1 inhibitor level is normal, but the protein is non- functional. In such cases, a functional assay for the inhibitor is essential to diagnosis. Diagnosis is important since mortality is high if the disorder is untreated. Treatment with the anabolic steroid danazol is effective. Therapy may be monitored by assays of C1 esterase inhibitor.

Inherited deficiencies of C1, C4, &, most commonly, C2 also occur. These deficiencies are associated with increased incidence of immune complex diseases such as systemic lupus erythematosus, Henoch-Schonlein purpura, polymyositis, & glomerulonephritis.

Acquired disease in serum complement levels may occur in either direction. Levels increase in acute phase reactions; they decrease in immune complex diseases because the classical pathway is activated so that consumption of complement proteins exceeds their synthesis. C3 & C4 are sometimes called 'subacute phase' proteins because the levels of these proteins rise at a later time than other acute phase proteins. Circulating levels of C3 & C4 reflect a balance between complement consumption due to immune complex formation & increased synthesis due to the acute phase response.

Immune complex diseases are disorders in which antigen-antibody complexes either are formed & deposited in tissues or are formed in the circulation & then become permanently attached to tissue cells. Measurement of complement components can be useful in the diagnosis of these diseases, because the Ag-Ab complexes activate the complement system. Hence, changes in the concentration of the complement components reflect the activity of the deposition process. Evidence for an active process consists of decreasing levels of C3 & C4 as well as the presence of C3 fragments in serum. C1q, often a part of antigen-antibody complexes, can also be measured. Laboratory results must be interpreted in context.

For example, inadequate preservation of the specimen will allow dissociation of C3 & C4 polymers. As a result, serum levels for C3 or C4 will be overestimated. A concurrent acute phase reaction in the patient will also affect C3 & C4 levels. In this case, extensive tissue damage releases proteolytic enzymes that cleave complement components that become detectable in the assays. In some cases, <A13275>immune complexes</A13275> are produced intermittently, & clinical symptoms may not have appeared or testing may not have been ordered until after the complement levels in serum have returned to normal.

Increases

• disseminated cytomegalovirus infection: C4 normal or increased, C3 very low,

Decreases

• systemic lupus erythematosus: C4 low, C3 sometimes low
• subacute bacterial endocarditis: both C3 & C4 low
• shunt nephritis: both C3 & C4 low
• gram-positive bacteremia: both C3 & C4 low

Specimen

No special patient preparation is required. 200 uL of serum. Store sample in freezer at -50 to -70 degrees C until ready for assay. Highly lipemic samples may result in inaccurate determination & should be redrawn on a fasting patient.

More general terms

• complement C4 in body fluid
• complement in serum

Additional terms

• complement-4 (C4)
• nephelometry

Component of

• connective tissue disease panel; collagen disease panel; SLE panel
• complement profile panel