Soluble Immune Checkpoints and Anti-HLA Antibodies in Kidney Transplant Recipients: Associations With Kidney Function

Kidney transplantation is the optimal treatment for end-stage renal disease. Soluble immune checkpoints (sICs) may serve as key immune regulators and potential biomarkers in transplantation. In this study, frozen serum samples from kidney transplant recipients (n = 30) at pre-transplantation (day 0) and post-transplantation (days 3 and 7), along with samples from healthy controls (HCs, n = 15), were analysed for sICs (sCD25, s4-1BB, sCD86, active TGF-β1, sCTLA-4, sPD-L1, sPD-1, sTIM-3, sLAG-3, galectin-9, sCD27, and sPD-L2) using a flow cytometry-based multiplex bead assay. To assess alloimmune sensitisation, anti-HLA panel-reactive antibody (PRA) levels were measured in transplant recipients. Kidney function was evaluated retrospectively by serum creatinine and estimated glomerular filtration rate (eGFR, CKD-EPI). All data were analysed to investigate their associations with kidney function. Pre-transplant patients had significantly higher serum levels of sCD25, sPD-L1, sTIM-3, Galectin-9, sCD27, and sPD-L2 compared to HCs. Post-transplant, sCD25, sPD-L1, sTIM-3, Galectin-9, sCD27, sPD-L2, and sCD86 showed significant temporal changes. Conversely, s4-1BB, sLAG-3, sCTLA-4, active TGF-β1, and sPD-1 levels showed no temporal changes and were comparable to HCs. Notably, PRA-positive patients exhibited higher sTIM-3 levels. Correlation and subgroup analyses based on eGFR revealed that higher levels sLAG-3 and sCTLA-4 levels were associated with better kidney function, while higher sCD25 and Galectin-9 levels were linked with poorer function. These findings suggest a link between sICs and renal function in the early post-transplant period, highlighting their potential as biomarkers and therapeutic targets. Future studies with larger cohorts are needed to evaluate their clinical utility in improving transplant outcomes.