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免疫抑制药物水平无法预测儿科移植患者的T细胞反应性。

Failure of immunosuppressive drug levels to predict T-cell reactivity in pediatric transplant patients.

作者信息

Sampson Valerie B, Dunn Stephen P, Rymeski Beth, Malatack James, Rong Nancy H, Flynn Louise, Krueger Leslie J

机构信息

Nemours Biomedical Research, Molecular Genetics, Cellular and Tissue Transplantation, Wilmington, DE 19803, USA.

出版信息

J Pediatr Surg. 2008 Jun;43(6):1134-41. doi: 10.1016/j.jpedsurg.2008.02.044.

DOI:10.1016/j.jpedsurg.2008.02.044
PMID:18558196
Abstract

PURPOSE

In children, therapeutic management of immunosuppression relies on allograft function, drug levels, and clinical insight. Using a Food and Drug Administration-approved test for T-cell response, T-cell activation in vitro can be measured to monitor the immune response.

METHODS

In a retrospective study, 92 posttransplant children who received either a liver and/or kidney transplant and were followed by routine screening had their T-cell response tested by the Cylex ImmuKnow assay (Columbia, MD). After phytohemagglutinin-L stimulation of T-cells, adenosine triphosphate (ATP) concentrations were measured. In this assay, light emission at lambda = 562 nm is proportional to the ATP concentration (ng/mL). Immunosuppressive drug trough levels were also measured. Quantitative real-time polymerase chain reaction Epstein-Barr virus (EBV) viral titers were determined for 2 patients.

RESULTS

Separating the results into younger than 12 years and 12-year or older populations, we found that for the younger than 12 years, 28% of patients were in the low immune function category, 47% in the moderate, and 25% in the high category. For the 12 years or older, 25% of patients were in the low immune function category, 47% in the moderate, and 28% in the high category. The immune function distribution was not different (P = not significant) between the younger than 12 years and 12-year or older groups. Tacrolimus trough levels were 6.3 +/- 2.4 ng/mL for younger than 12 years and 5.6 +/- 3.3 ng/mL for 12 years or older (P = not significant), and rapamycin was similar, but both showed no correlation to immune function. We observed increased ATP values with decreased EBV viral loads.

CONCLUSIONS

These results suggest that tacrolimus and/or rapamycin levels do not adequately determine the biologic effect of immunosuppression. We expect that future T-cell activation monitoring will allow us to diminish rejection and infection events posttransplantation and lead to a healthier pediatric transplant population.

摘要

目的

在儿童中,免疫抑制的治疗管理依赖于移植器官功能、药物水平和临床洞察力。使用美国食品药品监督管理局批准的检测T细胞反应的方法,可以测量体外T细胞活化以监测免疫反应。

方法

在一项回顾性研究中,对92名接受肝脏和/或肾脏移植并接受常规筛查的移植后儿童,通过Cylex ImmuKnow检测法(马里兰州哥伦比亚)检测其T细胞反应。在用植物血凝素-L刺激T细胞后,测量三磷酸腺苷(ATP)浓度。在该检测中,λ=562nm处的发光与ATP浓度(ng/mL)成正比。还测量了免疫抑制药物的谷浓度。对2例患者测定了定量实时聚合酶链反应爱泼斯坦-巴尔病毒(EBV)病毒滴度。

结果

将结果分为12岁以下和12岁及以上人群,我们发现12岁以下患者中,28%属于低免疫功能类别,47%属于中等免疫功能类别,25%属于高免疫功能类别。12岁及以上患者中,25%属于低免疫功能类别,47%属于中等免疫功能类别,28%属于高免疫功能类别。12岁以下和12岁及以上组之间的免疫功能分布无差异(P=无显著性)。12岁以下患者的他克莫司谷浓度为6.3±2.4 ng/mL,12岁及以上患者为5.6±

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