A series of circulating enzymatic serum proteins with nine functional components make up complement. Components of complement are labeled C1 through C9. The first four complement components are numbered out of sequence (in order of their discovery)—C1, C4, C2, and C3—but the remaining five are numbered sequentially.

When immunoglobulin (Ig) G or IgM reacts with antigens as part of an immune response, they activate C1, which then combines with C4, initiating the classic complement pathway, or cascade. (An alternative complement pathway involves the direct activation of C3 by the serum protein properdin, bypassing the initial components [C1, C4, C2] of the classic pathway.)

Complement then combines with the antigen-antibody complex and undergoes a sequence of reactions that amplify the immune response against the antigen. This complex process is called complement fixation.

Complement deficiency or dysfunction may increase susceptibility to infection due to defective phagocytosis of bacteria, for example. There may also be a relation to certain autoimmune disorders. Theoretically, any complement component may be deficient or dysfunctional, and many such disorders are being studied.

Primary complement deficiencies are rare. The most common ones are C2, C4, C6, and C8 deficiencies and C5 familial dysfunction.

More common secondary complement abnormalities have been confirmed in patients with lupus erythematosus, in some with dermatomyositis, in one with scleroderma (and in his
family), and in a few with gonococcal or meningococcal infections. The prognosis varies with the abnormality and the severity of associated diseases.