Elidemir Okan, Kancherla Binal S, Schecter Marc G, McKenzie E Dean, Morales David L, Heinle Jeffrey S, Mallory George B
Department of Pediatrics, Division of Pediatric Pulmonology, Texas Children's Hospital, Houston, TX 77030, USA.
Pediatr Transplant. 2009 Aug;13(5):606-10. doi: 10.1111/j.1399-3046.2008.01085.x. Epub 2008 Nov 9.
To investigate the clinical validity of newer diagnostic tests such as monitoring of EBVqPCR and lymphocyte function assay ImmuKnow in helping to diagnose PTLD in pediatric lung transplant recipients. Single-center, retrospective case-control study. CsA trough levels, EBVqPCR and ImmuKnow (Cyclex Inc., Columbia, MD, USA) levels were measured serially as part of routine care. Re-transplant patients and patients who did not reach 12 months post-transplant at the time of analysis were excluded. Twenty-seven patients met the inclusion criteria. The study group consisted of seven patients who developed PTLD, five of which were EBV- recipients who received EBV+ lungs. The rest of the eligible patients served as controls. Median time to develop PTLD was 273 days (range: 166-343). One, two, three, six, and nine months after transplant, mean (+/-s.d.) CsA trough whole blood levels (ng/mL) were not different between the two groups: 378 +/- 38, 390 +/- 52, 402 +/- 89, 359 +/- 42, and 342 +/- 115, vs. 416 +/- 105, 347 +/- 64, 337 +/- 78, 333 +/- 86, and 281 +/- 54 [PTLD vs. no-PTLD, respectively (p > 0.05 for all time points)]. Mean (+/-s.d.) EBVqPCR levels (copies/mL) measured at three, six, and nine months post-transplant were significantly elevated in PTLD group compared to no-PTLD group: 84 +/- 99, 3384 +/- 7428 and 839 +/- 1444 vs. 9 +/- 26, 8 +/- 36 and 32 +/- 136, respectively (p < 0.05 for all time points). Mean (+/-s.d.) ImmuKnow levels (ATP ng/mL) at three, six, and nine months post-transplant were significantly lower in the PTLD group when compared with no-PTLD group: 144 +/- 67, 137 +/- 110, and 120 +/- 153 vs. 290 +/- 161, 300 +/- 162, and 293 +/- 190, respectively (p < 0.05 for all time points). Close monitoring of EBV viral load by qPCR and the degree of immunosuppression via ImmuKnow may guide physicians to reach the diagnosis of PTLD early.
为研究诸如监测EBV定量聚合酶链反应(qPCR)和淋巴细胞功能检测ImmuKnow等新型诊断测试在帮助诊断小儿肺移植受者的移植后淋巴组织增生性疾病(PTLD)方面的临床有效性。单中心回顾性病例对照研究。作为常规护理的一部分,连续测量环孢素A(CsA)谷浓度、EBV qPCR和ImmuKnow(美国马里兰州哥伦比亚市Cyclex公司)水平。排除再次移植患者以及在分析时移植后未达12个月的患者。27例患者符合纳入标准。研究组由7例发生PTLD的患者组成,其中5例为接受EBV阳性供肺的EBV阴性受者。其余符合条件的患者作为对照。发生PTLD的中位时间为273天(范围:166 - 343天)。移植后1、2、3、6和9个月,两组间CsA谷全血水平(ng/mL)的均值(±标准差)无差异:分别为378±38、390±52、402±89、359±42和342±115,对比416±105、347±64、337±78、333±86和281±54 [分别为PTLD组与非PTLD组,所有时间点p>0.05]。移植后3、6和9个月测量的EBV qPCR水平均值(±标准差)(拷贝/mL)在PTLD组显著高于非PTLD组:分别为84±99、3384±7428和839±1444,对比9±26、8±36和32±136(所有时间点p<0.05)。移植后3、6和9个月PTLD组的ImmuKnow水平均值(±标准差)(ATP ng/mL)显著低于非PTLD组:分别为144±67、137±110和120±153,对比290±161、300±162和293±190(所有时间点p<0.05)。通过qPCR密切监测EBV病毒载量以及通过ImmuKnow监测免疫抑制程度可能有助于医生早期诊断PTLD。