BİNNAZ HANDAN ÖZDEMİR, BİLKAY BAŞTÜRK, CİHAT BURAK SAYIN, MEHMET HABERAL
Experimental and Clinical Transplantation - 2025;23(3):192-201
Objectives: Despite its known role in promoting tolerance, the function of programmed cell death protein 1/programmed death ligand 1 in antibodymediated rejection is less clear. We aimed to clarify this role by examining expression of programmed cell death protein 1/programmed death ligand 1 in renal allografts diagnosed with antibody-mediated rejection. Materials and Methods: We examined 110 patients: 68 with pure antibody-mediated rejection (group 1) and 42 with both antibody-mediated rejection and T-cell mediated rejection (group 2). Renal immune cell infiltration, cytokine expression, and programmed cell death protein 1/programmed death ligand 1 expression were examined immunohistochemically. Results: Expression of programmed cell death protein 1/programmed death ligand 1 in endothelial and inflammatory cells was higher in group 2 versus in group 1 (P < .001). Expression of programmed cell death protein 1/programmed death ligand 1 increased with immune cell infiltration. An inverse relationship existed between peritubular capillary DR expression and programmed cell death protein 1/programmed death ligand 1 interaction, with a positive correlation with tubular HLA-DR. Development of interstitial fibrosis was shown in 52.3% of patients with endothelial programmed cell death protein 1/programmed death ligand 1 interaction compared with 12.1% without this interaction (P < .001). Ten-year survival rate was 27.3% in patients with versus 66.7% in patients without endothelial programmed cell death protein 1/programmed death ligand 1 (P < .001) and 31.3% in patients with and 66.1% in patients without inflammatory cell programmed cell death protein 1/programmed death ligand 1 expression (P < .001). Conclusions: Heightened immunological nature in antibody-mediated rejection may influence the unexpected functions of programmed death ligand 1. Inhibitory functions of the programmed cell death protein 1/programmed death ligand 1 pathway may be less effective under strong T-cell activation with high immunological costimulation in antibodymediated rejection.
