Targeted salivary biomarkers for discrimination of periodontal health and disease(s)

Abstract

Generally, clinical parameters are used in dental practice for periodontal disease, yet several drawbacks exist with the clinical standards for addressing the needs of the public at large in determining the current status/progression of the disease, and requiring a significant amount of damage before these parameters can document disease. Therefore, a quick, easy and reliable method of assessing and monitoring periodontal disease should provide important diagnostic information that improves and speeds treatment decisions and moves the field closer to individualized point-of-care diagnostics.

Objective: This report provides results for a saliva-based diagnostic approach for periodontal health and disease based upon the abundance of salivary analytes coincident with disease, and the significant progress already made in the identification of discriminatory salivary biomarkers of periodontitis.

Methods: We evaluated biomarkers representing various phases of periodontitis initiation and progression (IL-1ß, IL-6, MMP-8, MIP-1α) in whole saliva from 209 subjects categorized with periodontal health, gingivitis, and periodontitis.

Results: Evaluation of the salivary analytes demonstrated utility for individual biomarkers to differentiate periodontitis from health. Inclusion of gingivitis patients into the analyses provided a more robust basis to estimate the value of each of these analytes. Various clinical and statistical approaches showed that pairs or panels of the analytes were able to increase the sensitivity and specificity for the identification of disease.

Conclusions: Salivary concentrations of IL-1ß, IL-6, MMP-8, MIP-1α alone and in combination are able to distinguish health from gingivitis and periodontitis. The data clearly demonstrated a heterogeneity in response profiles of these analytes that supports the need for refinement of the standard clinical classifications if we are to move toward precision/personalized dentistry for the twenty-first century.

Keywords: MMP-8; cytokines; periodontitis; personalized medicine; saliva.

Figure 1

Distribution of levels of IL-1ß (A), IL-6 (B), MMP-8 (C), and MIP-1α (D) in the three groups of subjects. Each point denotes the analyte value for a patient. The vertical red line denotes the group mean and the vertical blue dashed line denotes the threshold cutoff for each analyte (IL-1ß ≥ 28 pg/mL; IL-6 ≥ 5.5 pg/mL; MMP-8 ≥ 140 ng/mL; MIP-1α ≥ 5 pg/mL).

Figure 2

Correlation analyses of biomarkers IL-1ß (A), MMP-8 (B), and IL-6 (C) significantly related to clinical indices of periodontitis. Each point denotes a patient in the population (n = 209) and the line denotes the correlation trendline.

Figure 3

ROC analysis of individual salivary analytes in the entire population, comparing levels in periodontitis to those in “not periodontitis” (i.e., health and gingivitis).