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Unit Code 83391:
C4 Complement, Functional, Serum

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Useful For

Diagnosis of C4 deficiency

 

Investigation of a patient with an undetectable total complement

(CH50) level

Clinical Information

Complement proteins are components of the innate immune

system. There are 3 pathways to complement activation: 1) the

classic pathway, 2) the alternative (or properdin) pathway, and

3) the lectin activation (mannan-binding protein [MBP]) pathway.

The classic pathway of the complement system is composed of

a series of proteins that are activated in response to the presence

of immune complexes. The activation process results in the

generation of peptides that are chemotactic for neutrophils and

that bind to immune complexes and complement receptors. The

end result of the complement activation cascade is the formation

of the lytic membrane attack complex (MAC).

 

The absence of early components (C1-C4) of the complement

cascade results in the inability of immune complexes to activate

the cascade. Patients with deficiencies of the early complement

proteins are unable to generate the peptides that are necessary

clear immune complexes and to attract neutrophils or to generate

to lytic activity. These patients have increased susceptibility to

infections with encapsulated microorganisms. They may also have

symptoms that suggest autoimmune disease and complement

deficiency may be an etiologic factor in the development of

autoimmune disease.

 

Approximately 20 cases of C4 deficiency have been reported.

Most of  these patients have systemic lupus erythematosus (SLE)

or glomerulonephritis. Patients with C4 deficiency may also have

frequent bacterial infections.

 

Complement levels can be detected by antigen assays that

quantitate the amount of the protein (#8171 "Complement C4, Serum").

For most of the complement proteins, a small number of cases have

been described in which the protein is present but is non-functional.

These rare cases require a functional assay to detect the deficiency.

Reference Values

22-45 unit/mL

Interpretation

Low levels of complement may be due to inherited deficiencies,

acquired deficiencies, or due to complement consumption (e.g.,

as a consequence of infectious or autoimmune processes).

 

Absent C4 levels in the presence of normal C3 and C2 values

are consistent with a C4 deficiency.

 

Normal results indicate both normal C4 protein levels and normal

functional activity.

 

In hereditary angioedema, a disorder caused by C1 esterase inhibitor

deficiency, absent or low C4 and C2 values are seen in the presence

of normal C3 (due to activation and consumption of C4 and C2).

Cautions

The total complement assay (#8167 "Complement, Total, Serum")

should be used as a screen for suspected complement

deficiencies before ordering individual complement component

assays. A deficiency of an individual component of the complement

cascade will result in an undetectable total complement level.

 

Absent (or low) C4 functional levels in the presence of normal C4

antigen levels should be replicated with a new serum specimen to

confirm that C4 inactivation did not occur during shipping.

Clinical Reference

1.   Davis ML, Austin C, Messmer BL, et al:  IFCC-standardization

      pediatric reference intervals for 10 serum proteins using the

      Beckman Array 360 system. Clin Biochem 1996;29(5):489-492

 

2.   Gaither TA, Frank MM:  Complement. In Clinical Diagnosis and

      Management by Laboratory Methods. 17th edition. Edited by JB

      Henry. Philadelphia, WB Saunders Company, 1984, pp 879-892

 

3.   O'Neil KM:  Complement deficiency. Clin Rev in Allergy Immunol

      2000;19:83-108

 

4.   Frank MM:  Complement deficiencies. Pediatr Clin North Am

      2000;47:1339-1354

Key