Division of Cedars-Sinai Heart Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90048, USA.
J Heart Lung Transplant. 2010 May;29(5):504-8. doi: 10.1016/j.healun.2009.12.015. Epub 2010 Feb 4.
Balancing immunosuppression to prevent rejection while minimizing infection or drug toxicity risk is a major challenge in heart transplantation. Therapeutic drug monitoring alone is inadequate to measure the immune response. An immune monitoring (IM) assay (ImmuKnow; Cylex, Columbia, MD) performed on peripheral blood measures adenosine triphosphatase (ATP) release from activated lymphocytes and may predict the immune state. Therefore, we sought to determine the utility of IM in heart transplant recipients.
Between November 2005 and July 2008, 296 heart transplant recipients had a total of 864 IM assays performed at 2 weeks to 10 years post-transplant and were correlated with infection and rejection events that occurred within 1 month after IM testing. All patients received standard triple-drug immunosuppressive therapy with tacrolimus, mycophenolate mofetil and corticosteroids, without induction therapy.
There were 38 infectious episodes and 8 rejection episodes. The average IM score was significantly lower during infection than steady state (187 vs 280 ng ATP/ml, p < 0.001). The average IM score was not significantly different during rejection when compared with steady state (327 vs 280 ng ATP/ml, p = 0.35). Interestingly, 3 of 8 rejection episodes were antibody-mediated rejections and had hemodynamic compromise and, for these, the mean IM score was significantly higher than for steady-state patients (491 vs 280 ng ATP/ml, p < 0.001).
The non-invasive IM test appears to predict infectious risk in heart transplant patients. The association between high IM scores and rejection risk is inconclusive due to the small number of rejection episodes. Further studies with larger sample sizes for rejection episodes are required.
在心脏移植中，平衡免疫抑制以预防排斥反应，同时最大限度地降低感染或药物毒性风险是一项重大挑战。单独进行治疗药物监测不足以衡量免疫反应。外周血中的免疫监测（IM）检测（ImmuKnow；Cylex，哥伦比亚，MD）可测量激活淋巴细胞中三磷酸腺苷（ATP）的释放，并可能预测免疫状态。因此，我们试图确定 IM 在心脏移植受者中的应用价值。
2005 年 11 月至 2008 年 7 月，296 例心脏移植受者在移植后 2 周至 10 年内共进行了 864 次 IM 检测，并与 IM 检测后 1 个月内发生的感染和排斥反应事件相关联。所有患者均接受标准的三联免疫抑制治疗，包括他克莫司、霉酚酸酯和皮质类固醇，不进行诱导治疗。
发生 38 次感染事件和 8 次排斥反应事件。感染时的平均 IM 评分明显低于稳定状态（187 与 280 ng ATP/ml，p < 0.001）。与稳定状态相比，排斥反应时的平均 IM 评分无显著差异（327 与 280 ng ATP/ml，p = 0.35）。有趣的是，8 次排斥反应中有 3 次是抗体介导的排斥反应，且有血流动力学障碍，对于这些患者，平均 IM 评分明显高于稳定状态患者（491 与 280 ng ATP/ml，p < 0.001）。
非侵入性 IM 检测似乎可以预测心脏移植患者的感染风险。由于排斥反应事件数量较少，IM 评分与排斥反应风险之间的关联尚无定论。需要进一步进行更大规模的排斥反应事件样本量研究。
