Gingival crevicular fluid cGAS-STING pathway-related biomarkers are associated with periodontal disease severity and diagnostic performance

OBJECTIVE: To investigate gingival crevicular fluid (GCF) levels of stimulator of interferon genes (STING), 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP), and interferon-β (IFN-β) across periodontal health, gingivitis, and periodontitis. DESIGN: This study included 180 participants: 45 periodontally healthy individuals, 45 patients with gingivitis, 45 with Stage I-II periodontitis, and 45 with Stage III-IV periodontitis. GCF samples were collected for enzyme-linked immunosorbent assay (ELISA) measurement of STING, 2'3'-cGAMP, and IFN-β. RESULTS: GCF STING, 2'3'-cGAMP, and IFN-β levels increased from periodontal health to gingivitis, Stage I-II periodontitis, and Stage III-IV periodontitis. Correlation analysis showed that STING was positively correlated with 2'3'-cGAMP and IFN-β, and 2'3'-cGAMP was positively correlated with IFN-β. Within-group correlations between 2'3'-cGAMP and STING or IFN-β became more evident with increasing periodontal disease severity. In patients with periodontitis, these biomarkers were positively associated with clinical attachment loss to varying degrees. ROC analysis showed that the three-biomarker combined model yielded numerically higher AUCs than the individual biomarkers, with AUCs of 0.886 for distinguishing periodontitis from non-periodontitis and 0.949 for distinguishing Stage III-IV periodontitis from non-periodontitis. DeLong testing showed that statistically significant improvements over individual biomarkers were confined to selected comparisons. After adjustment for age, BMI, sex, and current smoking, higher levels of STING, 2'3'-cGAMP, and IFN-β remained independently associated with worsening periodontal status and increased periodontitis risk. CONCLUSION: GCF STING, 2'3'-cGAMP, and IFN-β were positively associated with periodontal disease severity, and their combined detection may serve as an adjunctive biomarker approach for periodontal assessment.