Background Sjögren's syndrome (SS) is a chronic autoimmune disease that causes salivary and lacrimal gland dysfunction, resulting in oral and ocular dryness. The pathogenesis of SS is still unknown. The Wingless (Wnt)/β-catenin pathway has been recently shown to play an important role in inflammation.
Objectives The aim of the present study was to determine serum and salivary levels of Dickkopf-related protein 1 (DKK1) and sclerostin those are inhibitor of Wnt/β-catenin signaling pathway and to evaluate the expression of Wnt-1 and Wnt-3a in the salivary gland, in patients with primary SS.
Methods 30 patients with primary SS, 30 patients with systemic lupus erythematosus (SLE) and 29 healthy controls were enrolled in the study. Fasting blood and saliva samples were obtained from the participants. Serum and salivary levels of DKK1 and sclerostin were measured by enzyme-linked immunosorbent assay. Wnt-1 and Wnt-3a expression were also immunohistochemically assessed in salivary gland. EULAR SS Disease Activity Index (ESSDAI), and EULAR SS Patient Reported Index (ESSPRI) in the SS group and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the SLE group were recorded.
Results Serum DKK1 and sclerostin levels were decreased in the SS and SLE groups compared to the controls (Table 1) (p<0.001 for both). Salivary sclerostin levels were similar among the study groups (p>0.05 for all). Salivary DKK1 levels were higher in the SS group compared to the control and SLE group (p=0.004 and p=0.009, respectively). Moreover, serum DKK1 level was higher in the SS group than in the SLE group (p=0.046). Serum DKK1 level was positively correlated with serum sclerostin level in the SS, SLE and control groups (r=0.677; p<0.001, r =0.783; p<0.001, and r=0.829; p<0.001, respectively). ESSPRI was negatively correlated with serum DKK1 and sclerostin levels (r=-0.363; p=0.049 and r=-0.416; p=0.022, respectively) in the SS group.
Moreover, in the salivary gland tissues, the positivities of Wnt-1 (71.4% vs. 46.2%, p=0.182) and Wnt-3a (71.4% vs. 53.8%, p=0.345) were relatively higher in the SS group compared to the control group, respectively.
Conclusions According to the best of our knowledge, this study is the first study evaluating the activity of Wnt/β-catenin pathway in the primary SS. The altered serum levels of DKK1 and sclerostin in primary SS and SLE is suggest that Wnt/β-catenin pathway is affected in these inflammatory diseases. Salivary DKK1 level is increased in primary SS in contrast to SLE. On the other hand, Wnt-1 and Wnt-3a expressions on the salivary gland are increased in primary SS. Therefore, it may be concluded that Wnt/β-catenin pathway acts pathogenic roles on the glandular inflammation.
Disclosure of Interest None declared