Complement and c4 null alleles in severe chronic adult periodontitis

Severe forms of chronic periodontitis affect up to 10% of adults. Tumour necrosis factor and lymphotoxin-alpha genes in the major histocompatibility complex are associated with severe periodontitis. Complement factor C4 is a nearby, polymorphic, functionally relevant gene region. Although associated with chronic mucosal infections, C4 deficiencies have not been assessed in adult periodontitis patients. We tested whether complement levels are systemically altered and C4 deficiencies associated with severe chronic periodontitis. In a case-control study, we analysed levels of plasma C3, and C4, serum classical pathway haemolytic activity, C4 allotypes and C4 gene numbers in 37 patients with severe chronic periodontitis and in 150 voluntary controls. Plasma levels of C3 were higher, and classical pathway haemolytic activity was lower in patients than in controls. Partial C4 gene deficiencies were more frequent in patients than in controls (odds ratio 2.4, 95% confidence interval 1.1-5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis.