C9 Complement, Functional, Serum
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).
Patients with deficiencies of the late complement proteins (C5, C6, C7, C8, and C9) are unable to form the MAC, and may have increased susceptibility to neisserial infections.
C9 deficiency is common in the Japanese population and has been reported to occur in almost 1% of the population. The lytic activity of C9-deficient serum is decreased. However, the assembly of C5b-C8 complexes will result in a transmembrane channel with lytic activity, although the lytic activity is reduced. Many C9-deficient patients are therefore asymptomatic. C9-deficient patients may, however, present with invasive neisserial infections.
Complement levels can be detected by antigen assays that quantitate the amount of the protein. 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.
Diagnosis of C9 deficiency
Investigation of a patient with a low total (hemolytic) complement (CH50) level
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 C9 levels in the presence of normal C3 and C4 values are consistent with a C9 deficiency. Absent C9 levels in the presence of low C3 and C4 values suggests complement consumption.
Normal results indicate both normal C9 protein levels and normal functional activity.
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) assay 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) C9 functional levels in the presence of normal C9 antigen levels should be replicated with a new serum specimen to confirm that C9 inactivation did not occur during shipping.
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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Sonntag J, Brandenburg U, Polzehl D, et al: Complement systems in healthy term newborns: reference values in umbilical cord blood. Pediatr Dev Pathol 1998;1:131-135
2. Prellner K, Sjoholm AG, Truedsson L: Concentrations of C1q, factor B, factor D and properdin in healthy children, and the age-related presence of circulating C1r-C1s complexes. Acta Paediatr Scand 1987;76:939-943
3. 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
4. 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
5. O'Neil KM: Complement deficiency. Clin Rev Allergy Immunol 2000;19:83-108
6. Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47(6):1339-1354