Gingival Crevicular Fluid Biomarkers During Periodontitis Progression and After Periodontal Treatment

Abstract

Objective: To identify gingival crevicular fluid (GCF)-derived inflammatory markers of periodontitis progression and periodontal treatment impact.

Methods: Periodontally healthy (H; n = 112) and periodontitis (P; n = 302) patients were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Levels of 64 biomarkers were measured in the GCF samples collected at each visit from progressing (n = 12 sites in H; n = 76 in P) and stable (n = 100 in H, n = 225 in P) sites. Clinical parameters and log-transformed analyte levels were averaged within clinical groups at each time point and analysed using linear mixed models.

Results: During monitoring, progressing sites had significantly higher levels of IL-1β, MMP-8, IL-12p40, EGF and VEGF. MMP-9 and Periostin were significantly more elevated in stable sites. Distinct cytokine profiles were observed based on baseline PD. Treatment led to significant reductions in Eotaxin, Flt-3L, GDF-15, GM-CSF, IL-1β, IL-17, MIP-1d, RANTES and sCD40L, and increases in IP-10 and MMP-9.

Conclusion: Distinct cytokine signatures observed in stable and progressing sites were maintained over time in the absence of treatment and significantly affected by NSPT.

Keywords: immunology; pathogenesis; periodontal diseases; therapy.

FIGURE 1

Line plots of mean (±SD) clinical attachment level (mm), mean pocket depth (mm) and mean percentage of sites presenting bleeding on probing (%BOP) in progressing (red) and stable (blue) sites. Clinical examination was performed bimonthly for 12 months, in the absence of treatment. Treatment was performed after the 12‐month visit (dotted line). (a) Progressing (n = 12) and stable (n = 12) sites from the same periodontally healthy participants. (b) Progressing (n = 76) and stable (n = 76) sites from the same periodontitis patients. (c) Shallow progressing (n = 40) and shallow stable (n = 40) sites from the same periodontitis patients. (d) Deep progressing (n = 9) and deep stable (n = 9) sites from the same periodontitis patients.

FIGURE 2

Line plots of mean (±SD) log‐transformed values for analytes over time. GCF samples were collected bimonthly for 12 months, in the absence of treatment in progressing (red) and stable (blue) sites. (a) Progressing (n = 12) and stable (n = 12) sites from the same periodontally healthy participants. (b) Progressing (n = 76) and stable (n = 76) sites from the same periodontitis patients. (c) Shallow progressing (n = 40) and shallow stable (n = 40) sites from the same Periodontitis patients. (d) Deep progressing (n = 9) and stable (n = 9) sites from the same periodontitis patients. Only analytes with effect size >0.3 are plotted. * indicates analytes that remained significantly different after FDR correction (q < 0.05).

FIGURE 3

Line plots of mean (±SD) log‐transformed analytes values before and after treatment. GCF at 12 and 6 months after treatment (18‐month visit) in progressing (red) and stable (blue) sites. (a) Progressing (n = 76) and stable (n = 76) sites from the same periodontitis patients. (b) Shallow progressing (n = 40) and shallow stable (n = 40) sites from the same periodontitis patients. (c) Deep progressing (n = 9) and deep stable (n = 9) sites from the same periodontitis patients. Only analytes with effect size >0.15 are plotted.

FIGURE 4

Line plots of mean (±SD) clinical attachment level (mm), mean pocket depth (mm) and mean percentage of sites presenting bleeding on probing (%BOP) in progressing (red) and stable (green) sites. Clinical examination was performed bimonthly for 12 months, in the absence of treatment. Treatment was performed after the 12‐month visit (dotted line). (a) Progressing (n = 12) and stable (n = 100) sites from different periodontally healthy participants. (b) Progressing (n = 76) and stable (n = 225) sites from different periodontitis patients. (c) Shallow progressing (n = 55) and shallow stable (n = 154) sites from different periodontitis patients. (d) Deep progressing (n = 19) and deep stable (n = 43) sites from different periodontitis patients.

FIGURE 5

Line plots of mean log‐transformed values for analytes over time. GCF samples were collected bimonthly for 12 months, in the absence of treatment in progressing (red) and stable (green) sites. (a) Progressing (n = 12) and stable (n = 100) sites from different periodontally healthy participants. (b) Progressing (n = 76) and stable (n = 225) sites from different periodontitis patients. (c) Shallow progressing (n = 55) and shallow stable (n = 154) sites from different periodontitis patients. (d) Deep progressing (n = 19) and deep stable (n = 43) sites from different periodontitis patients. Only effect size >0.3 are plotted; * indicates analytes that remained significantly different after FDR correction (q < 0.05).

FIGURE 6

Line plots of mean (±SD) log‐transformed analyte values before and after treatment. GCF at 12 and 6 months after treatment (18‐month visit) in progressing (red) and stable (green) sites. (a) Progressing (n = 76) and stable (n = 225) sites from different periodontitis patients. (b) Shallow progressing (n = 55) and shallow stable (n = 154) sites from different periodontitis patients. (c) Deep progressing (n = 19) and deep stable (n = 43) sites from different periodontitis patients. Only effect sizes >0.15 are plotted; * indicates cytokines that remained significantly different after FDR correction (q < 0.05).