Local and Plasma Biomarker Profiles in Localized Aggressive Periodontitis

Abstract

Localized aggressive periodontitis (LAP) patients possess a systemic hyperinflammatory response after lipopolysaccharide stimulation. However, the levels of inflammatory and bone biomarkers in plasma, as well as possible associations between local and plasma biomarkers, are unknown in LAP. This cross-sectional study aimed to characterize gingival crevicular fluid (GCF) and plasma biomarker profiles in LAP patients, their healthy siblings (HS), and healthy unrelated controls (HC). Fifty-eight LAP subjects, 33 HS, and 49 HC (African Americans, aged 5 to 25 y) were included. Following collection of clinical parameters with GCF and plasma samples, levels of 16 inflammatory and bone resorption biomarkers were determined with Milliplex. Univariate and correlation analyses were performed among all clinical and laboratorial parameters. Discriminant analyses were used to investigate groups of biomarkers discriminating LAP from HS and HC in GCF and plasma. GCF levels of multiple cytokines and chemokines and RANKL:OPG ratio (receptor activator of nuclear factor kappa-B ligand:osteoprotegerin) were higher in LAP disease, most of which positively correlated with probing depth and attachment loss of sampled sites. A group of IL-12p40, IL-6, IL-12p70, IL-2, and MIP-1α discriminated LAP diseased sites from twheir healthy sites, as well as from HS and HC healthy sites. In plasma, only RANKL levels were increased in LAP versus controls, which positively correlated with the percentage of affected sites and deep/bleeding sites. A plasma inflammatory profile including MIP-1α, IL-8, IL-10, and INF-γ could significantly discriminate LAP patients from HS and HC. No correlations were found between GCF and plasma levels of biomarkers. In conclusion, an inflammatory profile including groups of specific biomarkers in GCF and plasma may significantly discriminate LAP from healthy individuals. The hyperinflammatory response previously found in the peripheral blood of LAP patients is dependent on lipopolysaccharide stimulation, apparently resulting mostly in local tissue destruction and changes in biomarker profile, with a slight influence in the systemic inflammatory profile (ClinicalTrials.gov NCT01330719). Knowledge Transfer Statement: The results of this study can be possibly used by clinicians in the future as diagnostic tools for localized aggressive periodontitis. Thus, in the future, with proper consideration of cost, patient preference, chair-side feasibility and ultimately further studies validating the role of GCF markers for disease progression and response to treatment, this information could lead to more appropriate therapeutic decisions and the development of preventive approaches for susceptible patients.

Keywords: blood; bone resorption; cytokines; gingival crevicular fluid; inflammation; periodontal diseases.

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure.

Discriminatory potential of gingival crevicular fluid (GCF) and plasma biomarkers in localized aggressive periodontitis (LAP) subjects, their healthy siblings (HS), and unrelated healthy controls (HC). Principal component analysis identified subsets of highly correlated biomarkers produced in the GCF and plasma of patients (principal components, as shown in Table 5), which were further evaluated regarding their discriminatory potential by discriminant function analysis. Panels represent plots of significant separation in discriminant function analysis according to specific biomarker subsets among groups: (A) GCF: Note clear separation among LAP diseased sites (LAP-D) and LAP healthy sites (LAP-H) and then a more closely related profile (although still statistically different) for HS sites and HC sites by a biomarker group of IL-12p-40, IL-6, IL-12p70, IL-2, and MIP-1α (Wilks’s lambda <0.001 in canonical functions 1 and 2). (B) Plasma: Note less separation among the groups for the plasma inflammatory profile as compared with that of GCF, although there was a significant separation among LAP patients, their HS, and unrelated HC by a group of biomarkers consisting of MIP-1α, IL-8, IL-10, and IFN-γ (Wilks’s lambda = 0.012 in canonical function 1. *Significant biomarker in function 1. †Significant biomarker in function 2.