Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation
Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation
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DOI：
10.1111/j.1399-3062.2011.00626.x
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发表时间：
2011-06-01
影响因子：
2.6
通讯作者：
Mischak-Weissinger, E.
中科院分区：
文献类型：
--
作者：
Borchers, S.;Luther, S.;Mischak-Weissinger, E.
背景资料。巨细胞病毒(CMV)的再激活是异基因造血干细胞移植(HSCT)后发病率的主要原因。在健康个体中，病毒特异性T细胞(CMV-CTL)控制潜伏的CMV的重新激活。最近建立了用主要组织相容性复合体-I-肽复合体(四聚体)监测病毒表位结合的CD8(+)T细胞，从而能够评估HSCT后CMV-CTL的重建。为了通过CMV-CTL研究免疫重建和激活控制，我们对我科接受异基因HSCT的所有患者进行了为期2年的定期监测，这些患者至少匹配了6个商用四聚体中的一个人类白细胞抗原(HL A)类型。为了验证我们队列中巨细胞病毒再激活的危险因素，将过去10年内移植的所有患者的临床特征包括在统计分析中，以确定单次和复发巨细胞病毒再激活的相对风险。正如预期的那样，巨细胞病毒血清状态、人类白细胞抗原配型和供体来源显著影响巨细胞病毒复发再激活的风险。应用CMV-CTL四聚体监测2年，通过检测一组代表3种不同CMV蛋白6个表位的四聚体，可以监测134名患者中的114人(85%)。CMV-CTL在+50天前的存在和激活后的扩张似乎对CMV的再激活具有保护作用。受者巨细胞病毒阳性/供体阳性(R+/D+)组(91只/亩L)+100日平均巨细胞病毒-CTL数是R+/D-组(13只/亩L)和R-/D+组(2只/亩L)的5倍以上。在R+/D+组中，79%的患者在+100天内恢复了每亩L 10个CMV-CTL，而其他组中几乎50%的患者在那个时候未能产生CMV特异性应答(R+/D-：58%；R-/D+：43%)。四聚体监测可以帮助预测(复发)CMV再激活，是监测HSCT后复发再激活风险增加的个体患者的有用方法；因此，它可以帮助识别需要过继转移CMV-CTL的患者或优化抗病毒药物的使用。
Background. Reactivation of cytomegalovirus (CMV) is a major cause of morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). In healthy individuals, virus-specific Tcells (CMV-CTL) control the reactivation of latent CMV. The monitoring of virus-epitope-binding CD8(+) Tcells using major histocompatibility complex-I-peptide complexes (tetramers) has recently been established, allowing assessment of the reconstitution of CMV-CTL post HSCT.Patients and methods. In order to study immune reconstitution and reactivation control through CMV-CTL, we regularly monitored all patients undergoing allogeneic HSCT in our department for 2 years, who matched at least 1 of 6 commercially available tetramers for common human leukocyte antigen (HLA) types. To verify risk factors for CMV reactivations in our cohorts, clinical characteristics of all patients transplanted within the last 10 years were included in statistical analyses determining the relative risk for single and recurrent CMV reactivations.Results. As expected, CMV serostatus, HLA match, and donor source significantly influenced the risk of recurrent CMV reactivation. Applying CMV-CTL tetramer monitoring for 2 years allowed the monitoring of 114 (85%) of 134 patients, by testing a set of tetramers representing 6 epitopes from 3 different CMV proteins. The presence of CMV-CTL before day +50 and their expansion post reactivation seem to protect against recurrent CMV reactivations. The mean number of CMV-CTL by day +100 was >5-fold higher in the recipient CMV-positive/donor-positive (R+/D+) group (91/mu L) compared with the R+/D-(13/mu L) and the R-/D+ (2/mu L) group. Seventy-nine percent of patients from the R+/D+ setting recovered >10 CMV-CTL per mu L by day +100, while almost 50% of the other groups failed to mount a CMV-specific response by that time (R+/D- : 58%; R-/D+: 43%).Conclusion. Tetramer monitoring can help to predict (recurrent) CMV reactivation and is a useful approach to monitor individual patients with increased risk for recurrent reactivation post HSCT; thus, it could help to identify patients in need of adoptive transfer of CMV-CTL or to optimize the use of antiviral drugs.