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Diagnosis of C5 deficiency
Investigation of a patient with an absent total 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).
The absence of early components (C1-C4) of the complement cascade results in the inability of immune complexes to activate the cascade. Patients with deficiencies of the early complement proteins are unable to clear immune complexes or to generate lytic activity. These patients have increased susceptibility to infections with encapsulated microorganisms. They may also have symptoms that suggest autoimmune disease and complement deficiency may be an etiologic factor in the development of autoimmune disease.
More than 30 cases of C5 deficiency have been reported. Most of these patients have neisserial infections.
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 C5 levels in the presence of normal C3 and C4 values are consistent with a C5 deficiency. Absent C5 levels in the presence of low C3 and C4 values suggests complement consumption.
A small number of cases have been described in which the complement protein is present but is non functional. These rare cases require a functional assay to detect the deficiency C5FX / C5 Complement, Functional, Serum).
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.
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