Simultaneous assessment of complement components C3, C4, and B and their cleavage products in human gingival fluid

Abstract

The activation of the complement system is an important host‐mediated mechanism in the initiation and progression of inflammation. Complement cleavage products have been reported in gingival fluid obtained from periodontitis lesions suggesting a potential role for the activation of the alternative and/or classical complement pathways in the pathogenesis of periodontitis. Using the multi‐layer crossed immunoelectrophoresis technique, the effect of periodontal therapy on complement conversion of C3, C4, and B was assessed in 37 sites in 9 patients. Patients selected for study had moderate‐severe periodontitis as confirmed by clinical measurements of plaque, gingival inflammation, bleeding on probing, suppuration, pocket depth, and loss of attachment. Gingival fluid and clinical indices were obtained from representative sites prior to treatment and again 2–4 weeks following extensive periodontal scaling and root planing. Periodontal therapy resulted in a statistically significant decrease in all clinical parameters of inflammation. The percentage of C3 conversion decreased significantly from 70.0% to 37.5% with therapy (p=0.0001) while the reference protein, transferrin, did not significantly change. C4 conversion to C4c was never observed and total C4 was not significantly altered by therapy. Changes in B conversion to Bb could not be evaluated because the Bb precipitate was too small to measure reproducibly. These results suggested that complement activation, as measured by C3 conversion to C3c, decreased in gingival fluid following periodontal therapy and suggested a role for complement activation in the pathogenesis of inflammatory periodontal disease.

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches

“…Nevertheless, a role for C3 is supported by additional evidence: Induction of experimental gingivitis in human volunteers causes progressive elevation of complement activation (as determined by C3 conversion) correlating with increased clinical inflammatory parameters [81]. Conversely, the resolution of inflammation in periodontitis patients undergoing therapy leads to decreased complement activity, as revealed by reduced C3-to-C3c conversion in the GCF [86]. In a similar context, C3 is among the top 5% of genes that are most strongly downregulated following periodontal therapy [87].…”

Role of complement in host–microbe homeostasis of the periodontium

“…C3 is among the top 5% of genes that are most strongly downregulated following periodontal therapy [109]. Moreover, C3 conversion to C3c in GCF decreases dramatically after periodontal therapy [110]. Interestingly, a single nucleotide polymorphism of C5 (rs17611), which is associated with increased serum C5 levels and susceptibility to liver fibrosis (a complement-associated disease) [111], has been shown to be more prevalent in periodontitis patients than in healthy controls [112].…”

Antibody-dependent alternate pathway of complement activation in opsonophagocytosis of Porphyromonas gingivalis

“…However, some strains degrade complement components in the absence of factors essential for normal complement activation; moreover, they fail to bind C3b unless pretreated with protease inhibitors (25). Evidence for increased serum complement fragments in the crevicular fluid during periodontal breakdown (20,27) may provide in vivo relevance for such observations, although these studies do not distinguish physiologic cleavage from bacterial proteolysis. Despite the significant contribution of complement to the phagocytic process (9,24) and the unique interactions of P. gingivalis with complement (26,27), no studies to date have assessed the role of complement or the pathways of complement activation in opsonophagocytosis of P. gingivalis.…”