Tim-3 upregulation in monocyte subsets as a distinctive immune feature and early diagnostic indicator in systemic...

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by immune dysregulation. Tim-3 is an immune checkpoint receptor implicated in various autoimmune conditions. This study aimed to evaluate Tim-3 expression across monocyte subsets in newly diagnosed, treatment-naive SLE patients and assess its clinical relevance and diagnostic potential. Peripheral blood samples were analyzed using flow cytometry. Tim-3 expression and its co-expression with HLA-DR, DP, DQ, CD226, CD39, VNN2, and CD62L were assessed. Tim-3+ monocytes from healthy individuals displayed higher expression of HLA class II, VNN2, CD226, and CD39, but lower CD62L expression. In SLE patients, Tim-3 expression was significantly increased across all monocyte subsets compared with healthy controls, while VNN2 expression was reduced in Tim-3+ monocytes. Upon LPS stimulation, Tim-3+ monocyte subsets produced more TNF-α. The frequency of Tim-3+ monocytes positively correlated with anti-Ro52 and anti-SSA antibodies. ROC curve analysis demonstrated moderate diagnostic performance of Tim-3+ monocytes for SLE, with an area under the curve of 0.7901. Tim-3+ monocytes exhibit aberrant phenotypic and functional activation in SLE and are associated with disease-related autoantibodies. These findings highlight Tim-3+ monocytes as potential contributors to SLE pathogenesis and candidate biomarkers for early disease identification.