Salivary ACE2 Levels are Associated With Severity/Complexity of Periodontitis

Objectives: To access the association of soluble ACE2 and relating biomarkers in saliva/serum with oral/systemic conditions.
Methods: A total of 139 Chinese subjects (aged 35-75 years) were recruited at Prince Phillip Dental Hospital (PPDH), Hong Kong from November 2017 to February 2019 after screening and exclusion of common systemic comorbidities. Demographic, lifestyles, oral hygiene behaviors and mental/emotional states were questionnaired and recorded. Full-mouth periodontal examination was undertaken as well as saliva and blood samples were collected at PPDH. ELISA was performed to determine the levels of ACE2, MMP8 and TMPRSS2 in both saliva and serum. Total protein concentration was determined for adjusting ELISA results.
Results: The adjusted ACE2 levels of females in both saliva and serum (P<0.05, Mann-Whitney test) were significantly higher than those of males, but not saliva-to-serum ACE2 ratio. There was no such intersex notable difference in MMP8. The subjects were classified into three subgroups based on the new classification of periodontal conditions (2017), including periodontal health/gingivitis/Stages 1-2 periodontitis (Group 0-2), Stages 3-4 periodontitis/localized (Group 3/4L) and Stages 3-4 periodontitis/generalized (Group 3/4G). The adjusted salivary ACE2 levels of Group 3/4G were significantly higher than either Group 0-2 or 3/4L (P<0.05), while serum ACE2 levels of Group 0-2 were comparatively higher than the other two groups (P<0.05). Additionally, saliva-to-serum ACE2 ratios of Group 3/4G were greater than Group 0-2 (P<0.05). Moreover, the adjusted salivary MMP8 levels of Group 3/4G were significantly higher than Group 0-2. No significant difference for TMPRSS2 existed in either sample among the groups. There was significantly positive correlation between ACE2 and MMP8 in both saliva and serum (P<0.0001, ρSpearman: 0.65 and 0.43, respectively).
Conclusions: Salivary ACE2 levels and saliva-to-serum ACE2 ratios may reflect the overall severity and complexity of periodontitis.