Background/Purpose: Sjögren’s syndrome (SS) is known as autoimmune epithelitis, because epithelial cells in the glands are the primary target of disease and play a major role in pathogenesis of SS by mediating the development, maintenance and progression of the local autoimmune inflammatory response. Syndecan-1 (sdc-1), a transmembrane heparin sulfate proteoglycan, is predominantly expressed on epithelial cells and functions as coreceptors through binding to variant ligands. Furthermore, sdc-1 functions as soluble HSPG that can function as paracrine or autocrine effectors, or competitive inhibitors by ectodomain shedding. However, the expression and clinical significance of sdc-1 in patients with SS remain unclear. In this study, we investigated the expression of sdc-1 in minor salivary glands and association of syndecan-1 levels in plasma and saliva with disease activity and glandular functional parameters in SS patients.

Methods: We measured the levels of sdc-1 in plasma and unstimulated and stimulated saliva by ELISA and assessed the salivary flow rates in 70 SS patients and 26 normal controls. We also performed disease activity indexes, salivary gland scan, serologic markers and minor salivary gland biopsies in SS patients.

Results: Salivary gland tissue sections obtained from patients and normal controls were stained with monoclonal anit-sdc-1 antibody. Sdc-1 was up-regulated in ductal epithelial cells from patients and showed a more intense staining in severe inflamed glandular tissue. In specimen from patients, sdc-1 stain was also detected in infiltrating plasma cells as well as glandular epithelial cells. The mean unstimulated and stimulated salivary flow rates were significantly lower in patients than controls (p< 0.001). The levels of unstimulated salivary sdc-1 from patients were significantly higher than those from controls (p=0.003) and reversely correlated with unstimulated salivary flow rates (r=-0.358, p=0.032) and ejection fraction of parotid (r=-0.363, p=0.027) and submandibular glands (r=-0.485, p=0.002) on salivary gland scan. The levels of plasma sdc-1 were not different between patients with controls but showed a significant correlation with EULAR’s Sjögren’s Syndrome Disease Activity Index (r=0.507, p< 0.001) and EULAR’s Sjögren’s Syndrome Patient Reported Index (r=0.267, p=0.033). Minor salivary gland specimens included 68.3% with focus scores of ≥1 per 4mm2. Focus scores of ≥ 2 were significantly associated with higher levels of unstimulated salivary sdc-1, serum anti-Ro positivity and ocular stained scores and lower parotid gland functions on salivary gland scan. Those with higher levels of unstimulated salivary sdc-1 were 12.5 times (95% CI 1.76–88.74) more likely to have a focus score ≥2.

Conclusion: The levels of unstimulated salivary sdc-1 reflected the glandular function and degree of minor salivary gland inflammation. The levels of plasma sdc-1 showed a significant correlation with disease activity indexes in SS patients. These results suggested that the levels of unstimulated salivary and plasma sdc-1 are potential biomarkers for salivary glandular function and disease activity, respectively, in SS patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/syndecan-1-is-a-potential-biomarker-for-salivary-glandular-function-and-disease-activity-in-patients-with-sjogrens-syndrome/