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 (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.

C7 deficiency is relatively rare, over 50 cases have been described. The majority of C7 deficiency cases have neisserial infections, but cases with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and pyoderma gangrenosum have also been reported. The pathogenesis of the rheumatic disease is not clear.

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.