C6 Complement, Functional, Serum
Diagnosis of C6 deficiency
Investigation of a patient with an 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).
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.
A number of patients with C6 deficiency have been reported, and the majority of these patients are South African. Most of these patients have systemic meningococcal infection and some have had invasive gonococcal infections. Normal levels of C6 antigen have been reported in patients with dysfunctional C6 lytic activity.
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 C6 levels in the presence of normal C3 and C4 values are consistent with a C6 deficiency. Absent C6 levels in the presence of low C3 and C4 values suggests complement consumption.
Normal results indicate both normal C6 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) 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) C6 functional levels in the presence of normal C6 antigen levels should be replicated with a new serum specimen to confirm that C6 inactivation did not occur during shipping.
Clinical Reference 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