1 Department of Immunology, Institut Recerca Sant Pau Hospital, Barcelona, Spain. 2 Department of Immunology, Autonomous University of Barcelona, Barcelona, Spain. 3 Department of Cardiology, Sant Pau Hospital, Barcelona, Spain.
Transplantation. 2015 Jul;99(7):1521-8. doi: 10.1097/TP.0000000000000493.
Cardiac allograft vasculopathy (CAV) is a major limitation in long-term graft survival after heart transplantation (HTx). Its prediction and detection at an early stage is a challenge because an accurate, minimally invasive blood test is lacking. The aim of this study was to analyze the relationship of Tact (CD4CD45ROCD25-CD127) cells, Th1 cells, and thymus-derived regulatory (Treg) (CD4CD45ROCD25CD127) cells in peripheral blood with the development of CAV in HTx patients.
First, we performed a cross-sectional study in 29 patients at least 2 years after HTx, 17 with CAV and 12 without CAV. We then prospectively followed a group of 38 patients for 2 years immediately after HTx surgery. In both groups, we analyzed the relationship between CAV and the effector-to-regulatory T cell ratio.
In the cross-sectional study, patients with CAV showed statistically significant higher values of Th1-to-FoxP3Treg and Tact-to-CD127Treg ratios than non-CAV patients, with P less than 0.01 and P less than 0.001, respectively. Receiver operating characteristic curve analysis showed that the Tact:CD127Treg ratio was a potential biomarker of CAV, clearly discriminating CAV and non-CAV patients (area under curve [AUC] = 0.955; P = 0.001). In the prospective part of the study, we monitored the Th1:FoxP3Treg and Tact:CD127Treg ratios using the best tradeoff between anterior receiver operating characteristic sensitivity and specificity as a cutoff. Changes in the Tact:CD127Treg ratio were detected earlier than changes in the Th1:FoxP3Treg ratio. Both ratios were higher in HTx patients with CAV.
The Tact-to-Treg ratio is a valuable follow-up marker to detect HTx patients at risk of developing CAV.
心脏移植（HTx）后，心脏同种异体移植物血管病（CAV）是长期移植物存活的主要限制因素。由于缺乏准确的微创血液检测方法，因此早期预测和检测具有挑战性。本研究旨在分析外周血中 Tact（CD4+CD45RO+CD25-CD127）细胞、Th1 细胞和胸腺来源的调节性（Treg）（CD4+CD45RO+CD25+CD127）细胞与 HTx 患者 CAV 发展之间的关系。
首先，我们对至少在 HTx 后 2 年的 29 例患者进行了横断面研究，其中 17 例患者患有 CAV，12 例患者无 CAV。然后，我们对 38 例患者进行了 HTx 手术后立即进行的 2 年前瞻性随访。在这两组中，我们分析了 CAV 与效应细胞与调节性 T 细胞比值之间的关系。
在横断面研究中，患有 CAV 的患者的 Th1/FoxP3Treg 和 Tact/CD127Treg 比值明显高于无 CAV 患者，差异有统计学意义（P<0.01 和 P<0.001）。接受者操作特征曲线分析显示，Tact:CD127Treg 比值是 CAV 的潜在生物标志物，可清楚地区分 CAV 和非 CAV 患者（曲线下面积[AUC]为 0.955；P=0.001）。在研究的前瞻性部分，我们使用前后方接收者操作特征敏感性和特异性之间的最佳权衡作为截止值，监测 Th1/FoxP3Treg 和 Tact/CD127Treg 比值。Tact:CD127Treg 比值的变化比 Th1/FoxP3Treg 比值的变化更早被检测到。两种比值在患有 CAV 的 HTx 患者中均较高。
Tact:Treg 比值是一种有价值的随访标志物，可用于检测有发生 CAV 风险的 HTx 患者。
