Immune profiling of kidney transplant recipients: the role of Tribbles-1, Perforin, and Granzyme B in chronic humoral rejection.

Abstract

Introduction: For patients with end-stage renal disease (ESRD), kidney transplantation is the most effective treatment option, yet chronic antibody-mediated rejection (cAMR) remains a key challenge to long-term graft survival. Natural killer (NK) cells are implicated in allograft rejection, but their precise role remains unclear. This study assessed NK cell activity and the expression of Tribbles-1, Perforin, and Granzyme B in kidney transplant recipients with either stable grafts or cAMR.

Methods: Peripheral blood samples from 60 transplant recipients (30 stable grafts, 30 cAMR) were analyzed for NK cell percentages, activation (CD107a expression), and gene expression of Perforin, Granzyme B, and Tribbles-1 using real-time PCR.

Results: NK cell numbers were similar in both groups, likely due to the influence of immunosuppressive therapy. However, cAMR patients exhibited significantly higher CD107a expression, suggesting heightened NK cell activation, potentially due to suboptimal immunosuppressive dosing. While Perforin and Tribbles-1 expression showed no significant differences between the two groups, Granzyme B expression was higher in stable graft recipients than in those with cAMR.

Conclusion: These findings indicate that peripheral blood Granzyme B expression is not a specific biomarker for graft dysfunction, as elevated levels were also observed in stable graft recipients. Additionally, since Granzyme B is expressed in multiple immune cell types, its elevated levels in stable patients may indicate broader immune activation rather than graft dysfunction.

Clinical trial number: Not applicable.