Serum and salivary gland expression of S100A4 and S100A7 in Sjögren’s disease

S100A4 is a Ca 2 ⁺-binding protein involved in fibrosis, chronic inflammation, and immune cell migration and S100A7 is upregulated in response to inflammatory stimuli, leading to tissue accumulation of immune cells. We investigated whether serum and salivary gland S100A4 and S100A7 levels reflected immune activation and disease features in Sjögren’s disease (SjD). Serum S100A4 and S100A7 levels were measured by ELISA in patients with SjD ( n = 48), rheumatoid arthritis (RA; n = 20), and healthy controls (HCs; n = 18). Salivary gland S100A4 and S100A7 expression was evaluated by immunohistochemistry, and associations with clinical and immunologic features were analysed. Correlation analyses were adjusted for multiple testing using the Benjamini–Hochberg false discovery rate (FDR) procedure. Serum S100A4 levels were significantly higher in patients with SjD than in HCs, and S100A7 levels were higher in patients with SjD than in patients with RA or HCs. In patients with SjD, serum levels of S100A4 were correlated with ESR ( r = 0.48, p = 0.001), total protein ( r = 0.41, p = 0.004), CXCL11 ( r = 0.47, p = 0.001), and RF level ( r = 0.68, p < 0.001) with all associations remaining significant after FDR correction. Serum levels of S100A7 correlated with ESSDAI ( r = 0.43, p = 0.002) and serum levels of CXCL9 ( r = 0.48, p = 0.001), with both associations remaining significant after FDR correction. In the salivary glands, S100A7 was widely expressed, whereas S100A4 showed a more restricted distribution. S100A4-positive cell proportions showed several nominal clinical and immunologic associations, but none remained significant after FDR correction. S100A4 and S100A7 levels were elevated in SjD and were associated with disease activity measures and interferon-inducible chemokines, suggesting a possible association with interferon-related immune activation. Tissue-level associations with S100A4 require confirmation in larger studies.