Circadian Patterns of Salivary Flow in Sjogren's Disease

Abstract

Aim and Hypothesis: Salivary flow follows a circadian pattern and is influenced by clock genes, which also regulate Aquaporins (AQPs), water channels responsible for salivary flow regulation in salivary glands. A deficiency in AQP5 in mouse salivary glands disrupted this pattern. We hypothesized that patients with Sjögren's Disease (SjD) do not exhibit the same circadian salivary flow pattern as healthy controls. The study compared salivary flow patterns in healthy individuals and SjD patients. To do this, we assessed stimulated whole saliva (SWS) and unstimulated whole saliva (UWS) patterns in SjD subjects compared with healthy controls. Methods: Thirteen subjects per group were required to achieve 80% power. SjD subjects met the ACR/EULAR2016 criteria. During the first visit, participants provided consent. They received instructions for saliva collection at home at two time points (5 AM and 10 AM) for unstimulated whole saliva (UWS, 5 minutes) and stimulated whole saliva (SWS, 2 minutes), with a third sample collected on-site at 3 PM. Friedman's test compared salivary flow within each group across time points, while the Mann-Whitney U test compared salivary flow between groups. Generalized linear mixed models assessed group-time point interactions. Significance was set at α=0.05. Results: The study analyzed 13 healthy controls (10 female, 3 male, mean age 48.9 ± 10.7 years) and 13 SjD subjects (all female, mean age 65.3 ± 8.4 years). In SjD subjects, SWS 0.84 ± 0.83 mL/min, 1.08 ± 1.13 mL/min, and 1.00 ± 1.12 mL/min (p = 0.037) respectively. UWS ranged from 0.17 ± 0.21 mL/min at 5 AM to 0.24 ± 0.22 mL/min at 3 PM (p=0.46). No significant differences in control SWS; p = 0.527, with respective means of 2.80 ± 1.41 mL/min, 3.25 ± 1.81 mL/min, and 2.70 ± 1.42 mL/min. similar results were found in UWS: 1.03 ± 1.24 mL/min at 5 AM, 1.16 ± 1.34 mL/min at 10 AM, and 1.07 ± 1.29 mL/min at 3 PM (p = 0.527). SjD subjects iii had significantly lower UWS and SWS rates than healthy controls (p<0.001). No significant group interactions were observed (p>0.05). Conclusion: The data do not support the hypothesis that SjD subjects have an altered salivary flow pattern compared to healthy controls. Neither SWS nor UWS exhibited a clear circadian pattern in healthy individuals, suggesting a need for further research into circadian influences on salivary flow in the healthy population.