The genetics of the complement system.

It is suggested that the classical and alternative pathways of C3 activation and the terminal complement reaction pathway represent three replicates formed by gene duplication. It seems likely that the precursor system was what is now the alternative pathway and that its original function was a positive feedback loop for amplifying inflammatory reactions. These views are supported by physicochemical data on the complement components; by genetic data; and by similarities in the reaction patterns. Study of subjects with isolated complement component deficiencies provides information on the function of complement in vivo. It has been found that complement component deficiency is associated with bacterial infection, particularly with Neisseria; and even more so with immune complex disease. This second, rather surprising, association is likely to be the result of a requirement for complement in the catabolism of immune complexes on the one hand, and the need for an intact complement system to eliminate low virulence infectious organisms on the other.