Bhorade Sangeeta M, Janata Kelli, Vigneswaran Wickii T, Alex Charles G, Garrity Edward R
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
J Heart Lung Transplant. 2008 Sep;27(9):990-4. doi: 10.1016/j.healun.2008.06.005.
Current monitoring systems of immunosuppression in solid-organ transplant recipients are typically focused on prevention of clinical toxicities of immunosuppressive drugs. Unfortunately, these strategies are often not tailored to the individual and do not determine the optimal level of immunosuppression for these patients. Recently, the Cylex Immune Cell Function Assay (ImmuKnow; Cylex, Inc., Columbia, MD) was approved by the U.S. Food and Drug Administration (FDA) to measure global immune response in solid-organ transplant patients receiving immunosuppressive therapy. We sought to identify the level of functional immunity as measured by the ImmuKnow assay in lung transplant recipients and to correlate these values with the dose and trough levels of immunosuppression as well as other clinical parameters in lung transplant recipients.
We assessed the functional immune response by the ImmuKnow assay in 143 sequential blood samples from 57 lung transplant recipients from Loyola University Medical Center.
The average ImmuKnow assay in stable lung transplant recipients was 244 +/- 138 adenosine triphosphate (ATP) ng/ml and the median level was 236 ATP ng/ml (range 5 to 669 ATP ng/ml), approximately 703 +/- 695 days after lung transplantation. There was no correlation between ImmuKnow levels and tacrolimus trough levels. Stepwise multiple regression analysis identified African American race as an independent predictor of ImmuKnow assay levels when age, gender and underlying diagnosis were taken into account (p < 0.04). Fifteen infected lung transplant recipients had a lower ImmuKnow level at the time of their infections as compared with stable lung transplant recipients (111 +/- 83 vs 283 +/- 143 ATP ng/ml, respectively, p = 0.0001). Sixteen of the remaining 42 patients had low ImmuKnow assay values (<225 ATP ng/ml), but did not have active infection. There were only 2 patients with acute rejection of Grade A1 in this cohort. There were no identifiable associations of the ImmuKnow level with either acute rejection episode.
The Cylex ImmuKnow assay levels were lower in infected lung transplant recipients compared with non-infected recipients and increased with treatment of these infections. It remains unclear whether the ImmuKnow assay reflects over-immunosuppressed individuals at risk of infection or bone marrow suppression by infectious agents. Further investigation will determine the role of the ImmuKnow assay in tailoring immunosuppression in lung transplant recipients.
目前实体器官移植受者免疫抑制监测系统通常侧重于预防免疫抑制药物的临床毒性。不幸的是，这些策略往往没有针对个体进行调整，也没有确定这些患者的最佳免疫抑制水平。最近，Cylex免疫细胞功能检测（ImmuKnow；Cylex公司，马里兰州哥伦比亚）获得美国食品药品监督管理局（FDA）批准，用于测量接受免疫抑制治疗的实体器官移植患者的整体免疫反应。我们试图确定通过ImmuKnow检测法测量的肺移植受者的功能免疫水平，并将这些值与肺移植受者的免疫抑制剂量、谷浓度以及其他临床参数相关联。
我们对来自洛约拉大学医学中心的57名肺移植受者的143份连续血样进行了ImmuKnow检测法评估功能免疫反应。
在肺移植术后约703±695天，稳定的肺移植受者的ImmuKnow检测法平均水平为244±138三磷酸腺苷（ATP）ng/ml，中位数水平为236 ATP ng/ml（范围为5至669 ATP ng/ml）。ImmuKnow水平与他克莫司谷浓度之间无相关性。在考虑年龄、性别和基础诊断时，逐步多元回归分析确定非裔美国人种是ImmuKnow检测法水平的独立预测因素（p<0.04）。15名感染的肺移植受者在感染时的ImmuKnow水平低于稳定的肺移植受者（分别为111±83和283±143 ATP ng/ml，p = 0.0001）。其余42名患者中有16名ImmuKnow检测值较低（<225 ATP ng/ml），但没有活动性感染。该队列中只有2例A1级急性排斥反应患者。ImmuKnow水平与任何急性排斥反应事件均无明显关联。
与未感染的肺移植受者相比，感染的肺移植受者的Cylex ImmuKnow检测法水平较低，且随着这些感染的治疗而升高。目前尚不清楚ImmuKnow检测法是否反映了免疫抑制过度且有感染风险或因感染因子导致骨髓抑制的个体。进一步的研究将确定ImmuKnow检测法在调整肺移植受者免疫抑制方面的作用。
