Complement genetics and host defence

Abstract

There is a surprisingly high frequency of allelic variation in complement proteins. The best candidate for a true selective polymorphism is that of C3. For C4 and factor B within the MHC it is more difficult to identify the effects of individual alleles. No evidence suggests other alleles of C4 (and C2) than the null alleles (or the two isoproteins C4A and C4B) to have any functional differences with resistance. Thus, the major functions of complement, as shown by the effects of deficiency, are to resist infection against bacteria and particularly against Neisseria, and to prevent immune complex disease. There are also undoubtedly balancing contributions to the pathogenesis of some infections and to all immune complex disease. Data from studies of C4 polymorphism and from the presence of control proteins on micro-organisms suggest there may be in addition more subtle contributions to immunity against a variety of other infections.