Esmaeili Marzie, Afzali Shima, Dadfar Sepehr, Bonab Samad Farashi, Rahbar Maryam, Amirzargar Aliakbar, Haghmorad Dariush
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mol Biol Rep. 2025 Jun 9;52(1):573. doi: 10.1007/s11033-025-10688-9.
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.
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.
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.
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.
Not applicable.
对于终末期肾病（ESRD）患者，肾移植是最有效的治疗选择，但慢性抗体介导的排斥反应（cAMR）仍然是长期移植肾存活的关键挑战。自然杀伤（NK）细胞参与同种异体移植排斥反应，但其确切作用尚不清楚。本研究评估了移植肾功能稳定或发生cAMR的肾移植受者中NK细胞活性以及Tribbles-1、穿孔素和颗粒酶B的表达。
对60例移植受者（30例移植肾功能稳定，30例发生cAMR）的外周血样本进行分析，采用实时PCR检测NK细胞百分比、活化情况（CD107a表达）以及穿孔素、颗粒酶B和Tribbles-1的基因表达。
两组的NK细胞数量相似，可能是由于免疫抑制治疗的影响。然而，cAMR患者的CD107a表达显著更高，表明NK细胞活化增强，这可能是由于免疫抑制剂量不足所致。虽然两组之间穿孔素和Tribbles-1的表达无显著差异，但移植肾功能稳定的受者中颗粒酶B的表达高于发生cAMR的受者。
这些发现表明，外周血中颗粒酶B的表达不是移植肾功能障碍的特异性生物标志物，因为在移植肾功能稳定的受者中也观察到其水平升高。此外，由于颗粒酶B在多种免疫细胞类型中表达，其在移植肾功能稳定患者中的升高水平可能表明更广泛的免疫激活而非移植肾功能障碍。
不适用。
