Clinical Information

Complement (C) proteins are components of the innate immune system. There are 3 pathways to complement activation: the classical pathway, the alternative (or properdin) pathway, and 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 two 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 three main end products: anaphylatoxins which promote inflammation (C3a, C5a); opsonization peptides that are chemotactic for neutrophils (C3b) and facilitate phagocytosis; and the membrane attack complex (MAC), which promotes cell lysis.

The absence of early components (C1, C2, C3, 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 generate the peptides that are necessary to clear immune complexes and to attract neutrophils or to generate lytic activity. These patients have increased susceptibility to infections with encapsulated microorganisms. They may also have symptoms that suggest autoimmune disease; complement deficiency may be an etiologic factor in the development of autoimmune disease.

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.

Undetectable complement levels are found in patients with specific component deficiencies. Decreased complement levels are found in infectious and autoimmune diseases due to fixation and consumption of complement.