Complement in the pathophysiology and diagnosis of human diseases

Complement is a humoral effector system composed of 21 plasma proteins that was identified initially because of its cytolytic effects. In addition to cytolysis, complement has a number of different functions related to inflammatory and other host defense processes. The description of the reaction mechanism includes: (1) activation of the classical pathway through recognition of IgG and IgM antibodies by C1q, (2) activation of the alternative pathway which is usually achieved without participation of immunoglobulins, (3) generation of proteolytic enzymes composed of heteropolymers that cleave certain precursor proteins, (4) formation of the membrane attack complex (MAC), and (5) participation of control mechanisms. Methodologies for studying protein concentration and functional activities of complement components include not only the classical hemolytic techniques but also the extremely sensitive new radioimmunoassays and enzyme immunoassays for measuring the products of complement activation that are generated in vivo. Examples of genetically controlled complement deficiencies have been published for most complement components. The symptomatology of some of these patients serves to emphasize the protective role of complement. Acquired deficiencies are significant not only as laboratory aids in diagnosis and to evaluate the course of certain diseases, but also to indicate possible pathogenic disease mechanisms. Recently, it has been recognized that the complement proteins with genes located in the HLA region are polymorphic. Certain variants of proteins C2, C4, and factor B occur with higher frequencies in certain diseases than in the general population, which appears to be of great practical importance in laboratory medicine.