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Diagnosis of C9 deficiency
Investigation of a patient with a low total (hemolytic) complement (CH50) level
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.
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.
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.
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