Ege GÜRLÜ, Başak ARU, Müge BIÇAKÇIGİL KALAYCI, Gülderen YANIKKAYA DEMİREL
Turkish Journal of Immunology - 2026;14(1):24-34
Objective: The aim of this study was to assess serum levels of soluble immune checkpoint proteins (sICPs) in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) and to explore their association with disease activity. Materials and Methods: This preliminary cross-sectional study included 27 patients with SLE, 23 patients with SS, and 23 healthy controls. Serum concentrations of sCD25 (soluble interleukin-2 receptor alpha [IL-2Ralpha; CD25]), 4-1BB (tumor necrosis factor receptor superfamily member 9 [TNFRSF9; CD137]), B7.2 (CD86; cluster of differentiation 86), transforming growth factor beta 1 (TGF-beta1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene 3 (LAG-3), and Galectin-9 (Gal-9) were measured using a multiplex bead-based flow cytometric assay. Disease activity was evaluated using standard indices (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] for SLE; EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] for SS). Group differences were analyzed, and correlations between sICP levels and clinical indices were assessed. Results: Compared with healthy controls, SLE patients had significantly elevated levels of soluble TIM-3 (sTIM-3) (p<0.0001), sLAG-3 (p<0.0001), and Gal-9 (p<0.001). A strong positive correlation was observed between sGal-9 and sTIM-3 levels (r=0.79, p<0.0001), and a moderate correlation was observed between sGal-9 and sLAG-3 levels (r=0.55, p=0.002). In SS, sICP levels did not differ significantly from controls; however, sPD-1 correlated with sPD-L1 (r=0.56, p=0.004), and sGal-9 with sTIM-3 (r=0.54, p=0.007). ESSDAI scores in SS correlated with sCD25 (r=0.65, p=0.0007), sTIM-3 (r=0.49, p=0.01), and sGal-9 (r=0.41, p=0.04). Conclusion: Our findings suggest the potential use of sICPs as biomarkers in SLE and SS. However, larger studies are needed to validate the diagnostic and prognostic roles of these soluble checkpoints.
