Lee TC, Goss JA, Rooney CM, Heslop HE, Barshes NR, Caldwell YM, Gee AP, Scott JD, Savoldo B.
Michael E. DeBakey外科，贝勒医学院，休斯敦，德克萨斯 77030，美国
目标：导致淋巴细胞增生性疾病的EBV感染（Epstein-Barr Virus，一种疱疹病毒）是导致小儿原位肝移植（OLT）患者发病率的重要因素。我们在这里描述一种新型免疫检测法，该检测法能量化淋巴细胞免疫应答，并与EBV感染风险有关。
方法：2003年至2005年期间，我们前瞻性的收集了所有患者的数据，这项研究包括18名小儿肝移植患者（7名男性和11名女性），术后平均随访时间为47个月。我们应用实时定量PCR（qPCR）来检测患者的EBV负荷量，用淋巴细胞增殖刺激后CD3+的ATP释放量（ng/ml）来量化患者的免疫应答。根据EBV负荷量我们将患者分为：低（<1000 copies/microg DNA），中（1000-4000 copies/microg DNA），高（>4000 copies/microg DNA）。
结果：与EBV负荷量高于4000 copies/microg DNA的患者相比，EBV负荷量低的患者对PHA有更强的免疫应答(p < 0.04)。进一步的分析证明，ATP水平低于125 ng/mL的患者，其EBV剂量高于4000 copies/microg DNA的概率为100%；而ATP水平在125至400 ng/ml时概率为22%，大于400ng/ml时仅为15%（p < 0.05）。当免疫抑制降低时，我们观察到了与EBV病毒负荷量降低有关的ATP释放量增加。
结论：总之，该研究应用淋巴细胞活化检测法密切测量小儿肝移植受体的免疫抑制状况。由于以EBV DNA负荷量作为移植后淋巴增殖紊乱性疾病（PTLD）的单一参数阳性预测值较差，联合应用以上检测方法将有助于鉴别PTLD的高风险患者。
Clin Transplant. 2006 Nov-Dec;20(6):689-94.
Quantification of a low cellular immune response to aid in identification of pediatric liver transplant recipients at high-risk for EBV infection
Lee TC, Goss JA, Rooney CM, Heslop HE, Barshes NR, Caldwell YM, Gee AP, Scott JD, Savoldo B.
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
METHODS: All patient data were prospectively collected between 2003 and 2005. The study included 18 pediatric liver transplant recipients, seven males and 11 females with a mean follow-up of 47 months post-OLT. Patient EBV load was monitored using real-time quantitative PCR (qPCR).The ATP release (ng/mL) of CD3+ lymphocytes after mitogenic stimulation with phytohemagluttinin (PHA; Cylex Corporation) was used to quantitate patient immune response. Patients were stratified by EBV load: low (<1000 copies/microg DNA), medium (1000-4000 copies/microg DNA), and high (>4000 copies/microg DNA).
RESULTS: Patients with low EBV loads had a significantly (p < 0.04) stronger immune response to PHA than patients with EBV load >1000 copies/microg DNA. Further analysis demonstrated that patients with ATP level <125 ng/mL had 100% probability of an EBV titer >4000 copies/microg DNA, when compared with 22% if the ATP level was between 125 and 400 ng/mL or only 15% if >400 ng/mL (p < 0.05). When immunosuppression was reduced, we observed an increase of the ATP release that correlated with a decrease of the EBV viral load.
CONCLUSION: In conclusion, this study investigates the use of a lymphocyte activation assay to closely measure the immunosuppression status of pediatric liver transplant recipients.Because measurement of EBV DNA load as a single parameter has a poor positive predictive value for development of PTLD, the association of these assays may be of help in the identification of patients at risk for PTLD.
PMID: 17100717 [PubMed - indexed for MEDLINE]
OBJECTIVE: Uncontrolled EBV infection leading to lymphoproliferative disease is a significant cause of morbidity in pediatric orthotopic liver transplant (OLT) recipients. Herein, we describe the use of a novel immune assay, which quantifies the lymphocyte immune response and correlates the value to risk for EBV infection.PMID: 17100717 [PubMed - indexed for MEDLINE]
[责任编辑:刘 聪]
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