Expression of High Mobility Group Box 1 and Receptor for Advanced Glycation End Products in the Gingival Tissues of Periodontitis Patients with Type 2 Diabetes Mellitus

Abstract

Objective: Diabetes mellitus (DM) and periodontitis (PD) share similar pathophysiology including altered immune-inflammatory responses, and evidence implicates high mobility group box 1 (HMGB1)-receptor for advanced glycation end products (RAGE) axis in amplifying inflammation. Therefore, we aimed to investigate their expression in gingival tissues from individuals with Stage III/IV PD with and without type 2DM (T2DM). Materials and Methods: Thirty-three gingival tissue samples were taken from Group I: Systemically and periodontally healthy, Group II: Systemically healthy with PD and Group III: PD with T2DM. Tissue and gene expression were evaluated by immunohistochemistry and reverse transcription quantitative-polymerase chain reaction. The staining intensity distribution (SID) and the mean percentage of positive stained cells (MPPC) scores were reported. Results: When compared to group I, the gene expression of HMGB1 and RAGE were 2.85 and 2.50 times higher in PD+T2DM, respectively (p<0.001). MPPC and SID for HMGB1 and RAGE expression were high in Groups II and III, with increased expression in PD+T2DM. Furthermore, when compared to Group I, the expression was significantly higher (p<0.001). In the 33 samples, MPPC and SID scores for HMGB1 and RAGE in the epithelium and connective tissue significantly correlated with clinical parameters (p<0.001). With a diagnostic accuracy of 87.88% [95% confidence interval (CI): 72.67-95.18] and a positive and negative predictive value of 95% and 76.92%, respectively, HMGB1 was able to distinguish between periodontal health and disease. RAGE had a diagnostic accuracy of 93.94% (95% CI: 80.39-98.32) with a positive and negative predictive values of 91.67% and 100%, respectively. Conclusion: Increased HMGB1 and RAGE expression underscores their significance in amplifying inflammation in PD associated with T2DM. Furthermore, both can be used as diagnostic biomarkers.