GCF humoral immunity correlates with periodontal disease progression: A-prospective-study

Background: Aggregatibacter Actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe responsible for >90%subjects with aggressive periodontitis (AgP). A potent Aa virulence factor, CagE-homologue (CagE), was identified from studying alveolar bone loss-associated CD4+T cells via expression cloning, which can induce apoptosis of human cells. Objective: To understand the contribution of humoral immunity during periodontal disease progression, a longitudinal study was designed to monitor CagE-specific IgG immune responses in disease-free healthy (H), gingivitis (G) and AgP (P) patients (N=48: Power analysis). We hypothesized that clinical disease activity (i.e., loss of clinical attachment level-CAL >2mm) is associated with different magnitudes of CagE-specific IgG responses in H, G & P subjects. Materials & Methods: All subjects received a baseline periodontal examination including PI, GI, BI, PD, suppuration, tooth mobility and CAL, which was repeated every-3-months for 18-months. ELISA and Aa-specific RT-PCR were used to measure CagE-specific IgG in GCF and plaque samples, respectively. An ANOVA model with the group as fixed effects and subjects as random effects was used to test for associations. Results: Our analyses showed that: i) P subjects developed significantly more CAL (mean of all sites/full mouth: 0.83+/-0.92mm; p<0.05) than H & G (0.04-0.06+/-0.20mm); ii) among all Aa-infected pockets, when CAL<1mm there was a mean decrease of anti-CagE IgG level by -2.6ng/ml; conversely, there was a mean increase of CagE-specific IgG response by +3.0ng/ml when CAL>2mm (p=0.02). Thus, loss of CAL is significantly associated with the increase of anti-CagE IgG responses in GCF (p=0.02). In conclusion: These findings strongly suggest that the humoral Ab responses against virulent antigen(s) may be associated with active periodontal disease progression. Thus, anti-CagE immunity may have the potential to be a diagnostic indicator for Aa infection and Aa-associated disease activity. This project was supported in part by grants from University of Rochester & NIH-DE14473, USA