Clinical Information

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.