Pérez-Carrillo Lorena, González-Torrent Irene, Giménez-Escamilla Isaac, Delgado-Arija Marta, Benedicto Carlota, Portolés Manuel, Tarazón Estefanía, Roselló-Lletí Esther
Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IISLaFe), Valencia, Spain; Center for Biomedical Research Network on Cardiovascular Diseases, Madrid, Spain.
Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IISLaFe), Valencia, Spain; Center for Biomedical Research Network on Cardiovascular Diseases, Madrid, Spain. Electronic address: https://twitter.com/@DMTCIISLAFE.
J Heart Lung Transplant. 2025 Jun;44(6):894-904. doi: 10.1016/j.healun.2024.11.039. Epub 2024 Dec 7.
Liquid biopsy offers a potential alternative to decrease or eliminate endomyocardial biopsy for diagnosing allograft rejection. p-element-induced wimpy testis-interacting RNAs (piRNAs) are novel and promising disease biomarkers for their intrinsic characteristics such as stability in body fluids; however, their role in allograft rejection remains unexplored.
A training set based on small RNA sequencing technology was performed to identify piRNAs in endomyocardial tissue (n = 8) and serum samples (n = 40) from patients following heart transplantation. A validation set of the potential piRNAs identified in the training study was conducted in an independent larger cohort for the detection of acute cellular rejection (ACR, n = 105) and antibody-mediated rejection (AMR, n = 61).
We identified 20,292 piRNAs in endomyocardial tissue and 24,602 piRNAs in serum samples from patients following heart transplantation. We identified 7 piRNAs with a coincident expression profile in both types of samples and potential capacity for the noninvasive detection of cardiac rejection. Validation in a large independent cohort demonstrated that a panel of these piRNAs showed excellent performance for detecting grade ≥2R ACR (area under the receiver operating characteristic curve [AUC] = 0.819; p < 0.0001) and grade 1R ACR (AUC = 0.721; p = 0.001). Furthermore, our piRNA panel showed a potential discrimination ability of pAMR2 (AUC = 0.967; p < 0.0001).
To the best of knowledge, this study is the first to report the presence of piRNAs in both endomyocardial tissue and serum samples of patients after heart transplant, including their association with allograft rejection events. We propose a novel piRNA panel for the detection of cardiac allograft rejection.
液体活检为减少或消除用于诊断同种异体移植排斥反应的心内膜心肌活检提供了一种潜在的替代方法。p-元件诱导的弱小睾丸相互作用RNA（piRNA）因其在体液中的稳定性等内在特性，是新型且有前景的疾病生物标志物；然而，它们在同种异体移植排斥反应中的作用仍未被探索。
基于小RNA测序技术进行了一个训练集，以鉴定心脏移植患者的心内膜心肌组织（n = 8）和血清样本（n = 40）中的piRNA。在一个独立的更大队列中对训练研究中鉴定出的潜在piRNA进行验证集研究，以检测急性细胞排斥反应（ACR，n = 105）和抗体介导的排斥反应（AMR，n = 61）。
我们在心脏移植患者的心内膜心肌组织中鉴定出20,292个piRNA，在血清样本中鉴定出24,602个piRNA。我们在两种类型的样本中鉴定出7个具有一致表达谱且具有无创检测心脏排斥反应潜力的piRNA。在一个大型独立队列中的验证表明，一组这些piRNA在检测≥2R级ACR（受试者操作特征曲线下面积[AUC]=0.819；p<0.0001）和1R级ACR（AUC = 0.721；p = 0.001）方面表现出色。此外，我们的piRNA panel显示出对pAMR2的潜在鉴别能力（AUC = 0.967；p<0.0001）。
据我们所知，本研究首次报告了心脏移植患者的心内膜心肌组织和血清样本中存在piRNA，包括它们与同种异体移植排斥反应事件的关联。我们提出了一种用于检测心脏同种异体移植排斥反应的新型piRNA panel。
