TREM-1 Pathway Biomarkers for Classification of Periodontal Diseases and Monitoring of Treatment Response in Grade B and C Periodontitis

Abstract

Background: This study investigated the diagnostic potential of salivary triggering receptor expressed on myeloid cells (TREM)-1, peptidoglycan recognition protein 1 (PGLYRP1) and interleukin (IL)-1β for periodontitis patients and their ability to predict treatment outcome.

Methods: Systemically healthy, non-smokers with gingivitis (n = 31), stage III periodontitis (34 grade B: n = 34, grade C: n = 24) and healthy controls (n = 34) were recruited. Periodontitis patients (n = 42) underwent non-surgical periodontal treatment. Saliva was collected at baseline (T0) and post-treatment (T1, T3, T6). Biomarkers were measured using immunoassays. Periodontitis patients were categorised into responders (n = 19) and non-responders (n = 23) based on the number of residual pockets ≥ 5 mm with bleeding on probing at T6.

Results: TREM-1 was higher in periodontitis than in gingivitis and health, and in periodontitis grade B than in gingivitis (p < 0.05). PGLYRP1 and IL-1β were higher in periodontitis and gingivitis compared to controls (p < 0.01). All biomarkers discriminated periodontitis from health (AUC ≥ 0.9) with high sensitivity (82.1%-92.8%) and specificity (83.3%-88.9%). TREM-1 differentiated periodontitis from gingivitis (AUC = 0.72) with high sensitivity (92.8%) but low specificity (58.1%). Baseline biomarkers did not predict treatment outcome (AUC ≤ 0.61), while T1 levels showed moderate potential (AUC ≥ 0.71).

Conclusions: Salivary TREM-1 pathway biomarkers offer diagnostic value for periodontitis, are modulated by therapy but show limited ability to predict treatment outcome.

Study registration: The study has been registered in ClinicalTrials.gov (ID: NCT06715176, 4 December 2024).

Keywords: PGLYRP1; TREM‐1; periodontal treatment; periodontitis; saliva.

FIGURE 1

Salivary levels of TREM‐1, PGLYRP1 and IL‐1β in patients with different periodontal diagnoses. Levels of (A) TREM‐1, (B) PGLYRP1 and (C) IL‐1β in healthy (n = 34), gingivitis (n = 31) and periodontitis grade B (n = 34) and grade C (n = 24). (D) Spearman correlation coefficient between biomarkers and clinical variables. Kruskal–Wallis test with Dunn–Bonferroni post hoc test. *p < 0.05; **p < 0.01. Diagnostic accuracy of TREM‐1, PGLYRP1 and IL‐1β for discriminating between periodontitis and (E) healthy or (F) gingivitis. Diagnostic ability was measured by area under the receiver operator characteristic (AUC‐ROC), 95% confidence interval (CI), sensitivity (SN) and specificity (SP). Cut‐off for each biomarker is presented in the figure.

FIGURE 2

Effect of periodontal treatment on the salivary levels of TREM‐1, PGLYRP1 and IL‐1β in patients with grade B and grade C periodontitis. Levels of (A) TREM‐1, (B) PGLYRP1 and (C) IL‐1β before periodontal treatment and 1, 3 and 6 months after treatment in patients with periodontitis grade B (saliva: N = 17) and grade C (saliva: N = 19). Data are presented as mean ± SD. Differences within group were assessed using the Friedman and Dunn–Bonferroni post hoc test. Grade B: ^a p < 0.05 in comparison to baseline. Grade C: ^b p < 0.05 in comparison to baseline, ^c p < 0.05 in comparison to 1 month.

FIGURE 3

Salivary levels of TREM‐1, PGLYRP1 and IL‐1β in periodontitis patients according to their response to therapy. Levels of (A) TREM‐1, (B) PGLYRP1 and (C) IL‐1β in saliva before and after periodontal treatment in patients who responded (saliva: N = 17) or not respond to therapy (saliva: N = 19) at the end of the follow‐up. Data are presented as mean ± SD. Differences between groups were assessed using the Mann–Whitney test. *p < 0.05 in non‐responders compared to responders. Prognostic ability of TREM‐1, PGLYRP1 and IL‐1β in saliva measured at (D) baseline or (E) 1‐month post‐therapy for discriminating between responders and non‐responders at the end of the follow‐up. Prognostic ability was measured by area under the receiver operator characteristic (AUC‐ROC), 95% confidence interval (CI), sensitivity (SN) and specificity (SP). Cut‐off for each biomarker is presented in the figure. Non‐responders were those with > 4 sites with probing depth ≥ 5 mm and bleeding on probing 6 months after therapy.