Hyper-Responsive Trait among Children with Aggressive Periodontitis

The ‘hyper-responsive' trait refers to an increased inflammatory response by the immune system. The presence of bacterial antigens stimulates over-production of pro-inflammatory mediators resulting in tissue destruction. This phenotype has been identified in the innate immune system in diabetics. Objective: This study seeks to determine if this underlying defect in the immune response could cause an increased risk for periodontal disease. We hypothesize that patients with aggressive periodontal disease (AgP) have this hyper-responsive inflammatory trait which predisposes them to increased tissue destruction. Methods: Venous blood was collected from an African American cohort of AgP patients, ages 5-25, their healthy siblings, and healthy control participants. The ability to produce high level of cytokine that marks this trait was measured by stimulating participants' peripheral blood with ultrapure lipopolysaccharide (LPS) from E. coli or P. gingivalis. Luminex® assays were performed using the supernatents obtained. Results: Among the 22 cytokines analyzed by the Luminex® assay, four pro-inflammatory cytokines showed significant results: IFNγ, IL1α, IL2, and TNFα. AgP cultures stimulated with E. coli LPS had higher concentrations of all four cytokines when compared to healthy controls. Interestingly, healthy siblings demonstrated significantly higher levels of IL1a and IL2 when compared to the healthy controls, yet lower levels of IFNγ and TNFα than their AgP counterparts. Upon observation of this data, two distinct cytokine profiles existed within the AgP patients. Here, hyper-aggressive AgP patients concomitantly expressed significantly higher levels of IFNγ, IL1α, and IL2 when compared to those AgP with normal levels. Similar results were obtained from P. gingivalis LPS stimulated cultures. Conclusions: Our findings demonstrate the existence of hyper-responsive trait in AgP population, which can be induced in response to a periodontal pathogen and appears to have a genetic component. This research was supported by a UFCD Student Summer Research Fellowship and NIH U24 DE 016509-01.