Hyper-responsive phenotype in localized aggressive periodontitis

Abstract

The 'hyper-responsive' trait is an increased inflammatory response upon stimulation of innate immune receptors. Our objective was to determine if a hyper-reactive trait is present in a cohort diagnosed with aggressive periodontitis (LAgP). Peripheral blood was collected from 30 LAgP, 10 healthy unrelated, and 10 healthy sibling participants and stimulated with lipopolysaccharide (LPS) from E. coli and P. gingivalis. Cyto/chemokine response profiles were evaluated and analyzed by ANOVA. Elevated levels of pro-inflammatory cyto/chemokines were detected in E. coli and P. gingivalis LPS-stimulated LAgP cultures when compared with those of healthy unrelated control individuals. Periodontally healthy siblings presented with attenuated hyper-inflammatory cyto/chemokine profiles. Regression analysis demonstrated the hyper-reactive trait to be concomitant expression of pro-inflammatory cyto/chemokines and an absence of anti-inflammatory mediator expression. Our findings demonstrate hyper-responsive trait in a LAgP cohort, along with an attenuated hyper-responsiveness in healthy siblings, which can be induced in response to multiple TLR ligations.

Figures

Figure 1.

Representative clinical images of a localized aggressive periodontitis cohort. (a) Frontal smile photo. (b) Slight sign of marginal inflammation around teeth 9 and 25. Areas of enamel demineralization on canines, pre-molars, and molars. Probing depth of 4 mm on mesial-buccal aspect of tooth 9. Radiographic images of lower (c) and upper (d) anterior teeth show severe bone loss around tooth 25 (c) and 9 (d). Probing depth of 6 mm on mesial-buccal aspect of tooth 19, with no evident clinical signs of inflammation (e). Bite-wing radiographic images of right (f) and left (g) posterior teeth demonstrate severe vertical bone loss around all first molars and furcation involvement on lower first molars.

Figure 2.

Hyper-reactivity of peripheral blood cells to TLR4 ligation. Supernatants from TLR4-stimulated peripheral blood cells were used for cytokine detection. Persons with localized aggressive periodontitis (LAgP) (n = 30), healthy siblings (SIB), and healthy unrelated control individuals (CON) (n = 10). Box-plots show the median (horizontal line), inter-quartile range (box), 10th-90th percentiles (vertical lines). *p value < 0.001. #p value ≤ 0.008, LAgP vs. CON. ^p value ≤ 0.05, SIB vs. CON. ξp value ≤ 0.006, LAgP vs. SIB for the indicated cyto/chemokines.

Figure 3.

Hyper-reactivity of peripheral blood cells to TLR2 ligation. Supernatants from TLR2-stimulated peripheral blood cells were used for cytokine detection. Persons with localized aggressive periodontitis (LAgP) (n = 16), healthy unrelated control individuals (CON) (n = 10). Box-plots show the median (horizontal line), inter-quartile range (box), and 10th-90th percentiles (vertical lines).*p value < 0.0001. #p value < 0.005 LAgP vs. CON; ^p value ≤ 0.05 SIB vs. CON; ξp value ≤ 0.006 LAgP vs. SIB for indicated cyto/chemokines.