26511 C9 Complement, Functional, Serum (C9FX)

​​​​​​​C9, Complement C9, Functional C9, Functional C9 Complement, Hemolytic C9, Hemolytic C9 Complement, Ninth Component of Complement

​C9 Complement, Functional

​Diagnosis of C9 deficiency

Investigation of a patient with a low total (hemolytic) complement level

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

2. Centrifuge and aliquot serum into plastic vial.

3. Immediately freeze specimen

Gross lipemia

​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.

​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.

C9 deficiency is common in the Japanese population, (1:1000), but is otherwise rare. The lytic activity of C9-deficient serum is decreased. However, the assembly of C5b-C8 complexes will result in a transmembrane channel with minimal lytic activity. Many C9-deficient patients are 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 nonfunctional. These rare cases require a functional assay to detect the deficiency.

37-61 U/mL

​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.