Altundaş Necip, Balkan Eda, Kizilkaya Murat, Altunok Murat, Aksungur Nurhak, Kara Salih, Demirci Elif, Öztürk Gürkan
Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum, Türkiye.
Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Türkiye.
Medicine (Baltimore). 2025 Sep 5;104(36):e44271. doi: 10.1097/MD.0000000000044271.
Rejection following liver and kidney transplantation remains a major barrier to long-term graft survival. Early and reliable detection of rejection is crucial for optimizing patient outcomes and guiding personalized therapeutic approaches. Despite ongoing efforts, currently available serum-based biomarkers often fail to provide sufficient sensitivity and specificity for early diagnosis. Dickkopf-1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are molecules involved in Wnt signaling, immune regulation, fibrosis, and tissue remodeling. Their upregulation has been associated with inflammatory and fibrotic processes in various pathological contexts. These properties make them strong candidates as novel molecular biomarkers in transplant rejection. This prospective observational study aimed to investigate the association between DKK1 and CKAP4 mRNA expression levels and the occurrence of rejection in liver and kidney transplant recipients. Peripheral blood samples from 55 transplant patients diagnosed with rejection (30 kidney, 25 liver) and 35 healthy controls were analyzed for DKK1 and CKAP4 mRNA expression using real-time polymerase chain reaction. Expression profiles were evaluated in relation to clinical and histopathological parameters. DKK1 and CKAP4 mRNA expression levels were significantly elevated in transplant recipients with rejection compared with healthy controls. In kidney transplant patients, both markers showed increased expression, although no significant histopathological correlations were detected. In liver transplant recipients, DKK1 expression was significantly associated with cellular rejection and portal inflammation. These findings suggest that DKK1 and CKAP4 may serve as promising molecular biomarkers for transplant rejection monitoring. In particular, DKK1 may provide additional diagnostic value in identifying cellular rejection and portal inflammation in liver grafts. Further multicenter studies are required to validate these results and assess their potential for clinical application.
肝肾移植后的排斥反应仍然是长期移植物存活的主要障碍。早期且可靠地检测排斥反应对于优化患者预后和指导个性化治疗方法至关重要。尽管一直在努力,但目前可用的基于血清的生物标志物往往无法为早期诊断提供足够的敏感性和特异性。Dickkopf-1(DKK1)和细胞骨架相关蛋白4(CKAP4)是参与Wnt信号传导、免疫调节、纤维化和组织重塑的分子。它们的上调与各种病理情况下的炎症和纤维化过程有关。这些特性使它们成为移植排斥反应中新型分子生物标志物的有力候选者。这项前瞻性观察性研究旨在调查DKK1和CKAP4 mRNA表达水平与肝肾移植受者排斥反应发生之间的关联。使用实时聚合酶链反应分析了55例诊断为排斥反应的移植患者(30例肾移植,25例肝移植)和35例健康对照的外周血样本中DKK1和CKAP4 mRNA的表达。根据临床和组织病理学参数评估表达谱。与健康对照相比,发生排斥反应的移植受者中DKK1和CKAP4 mRNA表达水平显著升高。在肾移植患者中,两种标志物均显示表达增加,尽管未检测到显著的组织病理学相关性。在肝移植受者中,DKK1表达与细胞排斥反应和门静脉炎症显著相关。这些发现表明,DKK1和CKAP4可能作为移植排斥反应监测的有前景的分子生物标志物。特别是,DKK1在识别肝移植物中的细胞排斥反应和门静脉炎症方面可能提供额外的诊断价值。需要进一步的多中心研究来验证这些结果并评估其临床应用潜力。