Doesch Andreas O, Konstandin Mathias, Celik Sultan, Kristen Arnt, Frankenstein Lutz, Sack Falk-Udo, Schnabel Philipp, Schnitzler Paul, Katus Hugo A, Dengler Thomas J
Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
Transpl Int. 2008 Oct;21(10):963-71. doi: 10.1111/j.1432-2277.2008.00709.x. Epub 2008 Jun 24.
Development of Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real-time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty-seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1-16.9) years post-HTX]. In follow-up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 +/- 70.2 vs. 119.6 +/- 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.
爱泼斯坦-巴尔病毒(EBV)相关的移植后淋巴细胞增生性疾病(PTLD)的发生是心脏移植(HTX)后的一种严重并发症。本研究调查了成年心脏移植受者中的EBV DNA载量、其与免疫抑制的关联以及其作为PTLD发生标志物的潜力。通过定量实时聚合酶链反应(PCR)对172例稳定的HTX患者进行前瞻性测量EBV DNA载量。67例患者(占总数的39.0%)在初次检查时EBV PCR呈阳性[HTX后中位时间4.9年(范围1.1 - 16.9年)]。在6个月后对67例阳性患者的随访检测中,36例患者EBV PCR仍为阳性。EBV DNA的总体发生率与钙调神经磷酸酶抑制剂、硫唑嘌呤用药以及未使用霉酚酸酯(MMF)治疗显著相关。在初次检查时EBV DNA水平为阳性而复查时为阴性的患者中,发现初次检查时环孢素A水平显著更高(148.4±70.2 vs. 119.6±53.5 ng/ml,P < 0.05)。在研究过程中有3例患者(1.7%,3/172)被诊断为PTLD(平均随访4.0年)。EBV DNA病毒载量测定似乎对HTX后成人PTLD的风险预测或早期诊断无用,但证实了EBV DNA载量与定性和定量免疫抑制之间的关联。