C3 Complement, Functional, Serum
Diagnosis of C3 deficiency
Investigation of a patient with undetectable total complement (CH50) level
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 clear immune complexes or to generate 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.
C3 is at the entry point for all 3 activation pathways to activate the MAC. C3 deficiency may result in pneumococcal and neisserial infections as well as autoimmune diseases such as glomerulonephritis.
Complement levels can be detected by antigen assays that quantitate the amount of the protein (C3 / Complement C3, 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 Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Low levels of complement may be due to inherited deficiencies, acquired deficiencies, or due to complement consumption (eg, as a consequence of infectious or autoimmune processes).
Absent C3 levels in the presence of other normal complement values are consistent with a C3 deficiency.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The total complement (CH50) assay (COM / 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) C3 functional levels in the presence of normal C3 antigen levels should be replicated with a new serum specimen to confirm that C3 inactivation did not occur during shipping.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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 Allergy Immunol 2000;19:83-108
4. Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47(6):1339-1354