26508 C6 Complement, Functional, Serum (C6FX)

​C6, Complement, Functional C6, Functional Complement, Hemolytic C6, Hemolytic Complement, Sixth Component of Complement​​​

​Diagnosis of C6 deficiency

Investigation of a patient with an undetectable total complement level

The Total Complement 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. 

​1. Immediately after specimen collection, place the tube on wet ice.

2. Centrifuge and aliquot serum into plastic vial. 

​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.

​​Complement proteins are components of the innate immune system. There are 3 pathways to complement activation: 1) the classical pathway, 2) the alternative (or properdin) pathway, and 3) the lectin (mannan-binding lectin) pathway. The classical pathway of the complement system is composed of a series of proteins that are activated in response to the presence of immune complexes. A single IgM molecule or 2 IgG molecules are sufficient to trigger activation of the recognition complex initiated by C1q. The activation process triggers a cascade that includes an amplification loop. The amplification loop is mediated by C3, with cleavage of a series of proteins, and results in 3 main end products: 1) anaphylatoxins that promote inflammation (C3a, C5a), 2) opsonization peptides that are chemotactic for neutrophils (C3b) and facilitate phagocytosis, and 3) the membrane attack complex (MAC), which promotes cell lysis.​

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.

C6 deficiency is relatively rare, over 50 cases have been described. 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, hence the recommendation of functional testing.

​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.