Genetics of the complement system

Abstract

A large number of components have been identified in the complement system. Knowledge of their genetics comes from detection of genetic markers and studies of deficiency states in man and animals. Allotypes have been found for C3, C6 and Factor B. Population heterogeneity has also been reported for C4 but this is not inherited in a clearly Mendelian pattern. Factor B and C2 deficiency genes are linked to the HL A system in man, the latter showing a particular association with the haplotype 10, W18. In one family the C4 deficiency gene has been reported linked to the HL A haplotype 2 T3 W10. In studies of complement deficiencies the clinical effects were divided into 4 groups: patients who showed gross immunity deficiency to bacterial infection due to C3 deficiency; patients with C1, C2 and C4 deficiency: of the C2 deficient subjects half were in good health and the other half had systemic lupus erythematosus (SLE), Henoch Schonlein purpura, polymyositis and glomerulonephritis; subjects with C1 and C4 deficiency also had manifestations of SLE; patients with C5, C6 and C7 deficiency, a11 healthy except one who had SLE; patients with angioneurotic edema associated with C1 inhibitor deficiency. At present the clearest role of the complement system is in resistance to infection. There is no evidence that genetic complement deficiency interferes with antibody formation or with generation of tolerance. (Myrianthopoulos - Bethesda, Md.)