Heikal N M, Bader F M, Martins T B, Pavlov I Y, Wilson A R, Barakat M, Stehlik J, Kfoury A G, Gilbert E M, Delgado J C, Hill H R
ARUP Institute for Clinical and Experimental Pathology, University of Utah school of Medicine, Salt Lake City, Utah 84132, USA.
Transplant Proc. 2013 Jan-Feb;45(1):376-82. doi: 10.1016/j.transproceed.2012.04.034. Epub 2012 Sep 18.
Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients.
We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials.
We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001).
Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies.
排斥反应、心脏移植血管病变（CAV）和感染是心脏移植受者死亡的重要原因。评估特定患者的免疫状态仍然具有挑战性。尽管心内膜心肌活检（EMB）和血管造影分别对识别排斥反应和CAV有效，但这些方法昂贵、具有侵入性且可能有许多并发症。本研究的目的是评估免疫功能并评估其在预测心脏移植受者排斥反应、CAV和感染方面的效用。
我们在常规EMB时以及临床指示时前瞻性地获取样本，用于测量免疫状态检测（IM）、12种细胞因子和可溶性CD30（sCD30）。对EMB标本进行急性细胞排斥反应和抗体介导的排斥反应（AMR）评估。通过血管造影冠状动脉疾病的发生来诊断CAV。通过阳性细菌或真菌培养物和/或病毒血症的存在来识别检测后接下来30天内发生的感染事件，这些感染事件促使使用抗菌药物进行治疗。
我们从56名心脏移植受者中收集了162份样本。有31次感染事件、7例AMR和4例CAV病例。感染期间的平均IM值显著较低，（P = 0.04）。可溶性CD30浓度与感染事件呈显著正相关，（P = 0.001）。白细胞介素-5（IL-5）与AMR事件之间观察到显著正相关（P = 0.008）。肿瘤坏死因子-α和IL-8与CAV呈显著正相关（P = 0.001）。
免疫功能监测在预测心脏移植受者的排斥反应、CAV和感染方面似乎很有前景。这种方法可能有助于实现更个体化的免疫抑制，还可能减少不必要的心内膜心肌活检和心脏血管造影。
