Distinct molecular profile in Sjögren's syndrome is associated with disease activity and clinical manifestations.

Sjögren's disease (SjD) is a systemic autoimmune condition for which reliable diagnostic and stratification biomarkers are still lacking. Several molecules have been implicated in its pathogenesis, and this study aimed to evaluate their potential as biomarkers in a monocentric cohort of SjD patients. Sera from 40 SjD patients (2016 ACR/EULAR criteria) and 41 matched controls were analyzed for 23 soluble inflammatory mediators using a Luminex® multiplex immunoassay. Clinical and laboratory correlations were examined, and multivariate logistic regression was performed. Compared with controls, SjD patients had significantly higher levels of IL-15 (11.52 ± 24.95 vs. 1.37 ± 1.26 pg/ml, P = 0.0009), monocyte chemoattractant protein (MCP)-1 (683.6 ± 1127 vs. 654.8 ± 608.9 pg/ml, P = 0.0203), TNFRII (8588 ± 2889 vs. 5505 ± 1007 pg/ml, P < 0.0001), and MMP-8 (6382 ± 12,697 vs. 6247 ± 6950 pg/ml, P = 0.0141), while IL-1RII was reduced (6267 ± 1699 vs. 8514 ± 2255 pg/ml, P < 0.0001). IL-15 correlated with hypergammaglobulinemia and monoclonal component, MCP-1 with focus score and sicca severity, and IL-1RII with anti-SSB positivity. Logistic regression identified TNFRII and IL-1RII as the strongest independent predictors of SjD (AUC = 0.89). This study supports the association of IL-15, TNFRII, and MCP-1 with immune dysregulation in SjD and highlights MMP-8 and IL-1RII as promising serological biomarkers. Validation in larger, longitudinal cohorts is warranted.