Background/Purpose: Patients with Sjögren’s syndrome (SS) suffer from significantly reduced saliva production. Saliva is important for oral health. A careful of sodium, chloride, potassium and phosphate ions in saliva is essential for this. Studies have suggested that salivary levels of sodium are increased in SS patients but no mechanism for the increased sodium has been suggested. We aimed to perform an extensive characterization of sialochemical parameters in SS patient saliva compared to non-SS sicca patients, correlate this with SS histopathology, and investigate potential mechanisms underpinning any differences observed.

Methods: Unstimulated and stimulated submandibular/sublingual (SmSl), and stimulated parotid (Par) saliva was collected from 32 SS patients diagnosed according to the 2016 ACR-EULAR criteria. For comparison, 62 non-SS sicca control patients were analysed. Sodium, chloride, phosphate and potassium ion concentration, α-amylase activity and total protein content were measured as sialochemical parameters. CD45, CD20 and CD3 percentage positive cell area in parotid biopsies were quantified, and determination of lymphoepithelial lesion (LEL) severity was carried out as published (1,2). Epithelial sodium channel (ENaC) immunostaining was performed according to standard protocols.

Results: Sodium concentrations were significantly higher in unstimulated SmSl (p< 0.0001), stimulated SmSl (p=0.002), and stimulated Par saliva (p< 0.0001) of pSS patients, compared to non-SS controls (Fig1A). No other sialochemical readout was so significantly different between in saliva from pSS and controls. Stimulated Par saliva sodium levels positively correlated with the percentage of CD45⁺ infiltration (r=0.69, p< 0.001; Fig1B) and CD20⁺ B cells in pSS patient parotid glands (r=0.73, p< 0.0001; Fig1C) and maximum LEL severity score (r=0.46, p=0.02; Fig1D) in patient parotid glands. Percentage area of CD3⁺ T cells were only fairly correlated with salivary sodium (r=0.23, p=0.015). No significant correlation between other sialochemical parameters and infiltration was observed. In non-SS control parotid tissue, ENaC, responsible for transport of sodium out of saliva, into ductal cells, was clearly localized at the apical membrane of the luminal striated duct cells (Fig1E,F). In tissue from SS patients with a positive FS, and SS patients with positive FS and presence of LELs, ENaC appeared to be absent from the apical membrane of the ductal cells (Fig1G,H).

Conclusion: We confirm that salivary sodium levels are increased in patients with SS and extend this observation by correlating these levels with the percentage of CD45⁺ and CD20⁺ infiltration. In SG tissue of SS patients with inflammatory foci (with and without LELs), the ENaC protein does not appear to be present at the apical membrane of the ductal cells. We hypothesize that B cell-related cytokines in SS are directly responsible for the dysregulation of sodium transport channels in SS and may represent a larger driving force behind decreased oral health in SS patients than previously appreciated.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/salivary-sodium-levels-in-the-parotid-salivary-gland-of-ss-patients-suggest-b-cell-mediated-epithelial-sodium-channel-disruption/