Barkholt Lisbeth, Linde Annika, Falk Kerstin I
Department of Clinical immunology, Division of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Transpl Int. 2005 Jul;18(7):835-43. doi: 10.1111/j.1432-2277.2005.00145.x.
The development of Epstein-Barr virus (EBV) associated lymphoproliferative disorder (PTLD) is related to EBV genome numbers in serum or plasma and B-cells, and the level of immunosuppression. EBV DNA viremia, defined as presence of EBV genomes in serum or plasma, is common in immunodeficiency. This survey of EBV viremia was performed by real-time polymerase chain reaction (PCR) on consecutive serum samples of 21 patients with acute (n = 3) or chronic liver disease (n = 18) during the first year after liver transplantation (LTX). Cytomegalovirus (CMV) DNA was analyzed with PCR in serum or leukocytes. The levels of EBV and CMV viremia were related to PTLD and the effect of different anti-rejection regimens. All patients were EBV-seropositive pre-LTX. In total, 24 of 152 (16%) samples from 10 of 21 (48%) individuals were EBV positive [five of 11 cyclosporin A (CsA); five of 10 tacrolimus treated cases]. EBV viremia was demonstrated in five of seven patients with OKT3 therapy. The number of EBV DNA positive samples was highest (26%) at 14 days after LTX. In the OKT3 treated groups, the medians of EBV DNA copy numbers were 1600/ml (range 230-7200) and 380/ml (range 120-860) in the CsA and tacrolimus patients, respectively (P < 0.02). One patient developed EBV lymphoma and another one EBV hepatitis 13 months and 24 days post-LTX, respectively. Both patients had received OKT3. Their EBV genome load was not significantly different from what was found in other patients. After ganciclovir therapy, EBV DNA was eradicated from serum in four of five patients for several months. EBV DNA load was not affected by CMV infection or disease. We conclude that presence of EBV in serum is a possible marker of an active infection and an early ganciclovir therapy may be beneficial. Quantification of EBV load offers the potential to implement pre-emptive interventions.
爱泼斯坦-巴尔病毒（EBV）相关淋巴增殖性疾病（PTLD）的发生与血清或血浆以及B细胞中的EBV基因组数量和免疫抑制水平有关。EBV DNA病毒血症，即血清或血浆中存在EBV基因组，在免疫缺陷患者中很常见。本研究采用实时聚合酶链反应（PCR）对21例肝移植（LTX）术后第一年的急性（n = 3）或慢性肝病（n = 18）患者的连续血清样本进行EBV病毒血症检测。同时采用PCR分析血清或白细胞中的巨细胞病毒（CMV）DNA。EBV和CMV病毒血症水平与PTLD以及不同抗排斥方案的效果相关。所有患者肝移植术前均为EBV血清学阳性。21例患者中有10例（48%）的152份样本中有24份（16%）EBV呈阳性[11例环孢素A（CsA）治疗患者中有5例；10例他克莫司治疗患者中有5例]。7例接受OKT3治疗的患者中有5例出现EBV病毒血症。肝移植术后14天时，EBV DNA阳性样本数量最高（26%）。在接受OKT3治疗的组中，CsA治疗患者和他克莫司治疗患者的EBV DNA拷贝数中位数分别为1600/ml（范围230 - 7200）和380/ml（范围120 - 860）（P < 0.02）。1例患者在肝移植术后13个月发生EBV淋巴瘤，另1例在术后24天发生EBV肝炎。这两名患者均接受过OKT3治疗。他们的EBV基因组载量与其他患者相比无显著差异。更昔洛韦治疗后，5例患者中有4例血清中的EBV DNA在数月内被清除。EBV DNA载量不受CMV感染或疾病的影响。我们得出结论，血清中EBV的存在可能是活动性感染的标志物，早期更昔洛韦治疗可能有益。EBV载量的定量分析为实施抢先干预提供了可能。
