C3, Complement, Functional C3, Functional Complement, Hemolytic C3, Hemolytic Complement, Third Component of Complement
C3 Complement, Functional
Diagnosis of C3 deficiency
Investigation of a patient with 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.
3. Immediately freeze specimen.
Absent (or low) C3 functional levels in the presence of normal C3 antigen levels should be replicated with a new serum specimen to confirm that C3 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 (or 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.
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 in which complement deficiency may be an etiologic factor.
C3 is at the entry point for all 3 activation pathways to activate the MAC. C3 deficiency may result in severe and recurrent pneumococcal and neisserial infections. Deficiency is very rare, with less than 30 cases described.
Complement levels can be detected by antigen assays that quantitate the amount of the protein (C3 / Complement C3, Serum). 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.
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 C3 levels in the presence of other normal complement values are consistent with a C3 deficiency.