The Regulatory/Cytotoxic T Cell Profiles in Blood of Pediatric Kidney-Transplant Recipients with Acute Rejection

F. Fadel, Manal F Elshamaa, Mostafa El-Ahmady, R. Galal, Mona H. Ibrahim, S. Kamel, D. Kandil, D. A. A. Haleem
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Abstract

Background: The equilibrium between regulatory cells and cytotoxic cells may define graft consequence. We investigated the relationship between the expression of main regulatory and cytotoxic markers (i.e., FOXP3 and granzyme B (GZM-B), respectively) and acute rejection (AR) in the peripheral blood of pediatric renal transplant recipients. Methods: In this retrospective study, FOXP3 mRNA expression and serum GZM-B levels in peripheral blood samples from 47 first-time pediatric kidney-transplant recipients were measured, with 17 children classified as possessing AR; whereas the remaining 30 children had functionally stabilized allografts. Results: Levels of the FOXP3 mRNA vs. the expression levels GADPH mRNA (FOXP3 mRNA/GADPH mRNA) were significantly elevated in children with AR than those with stabilized renal allograft (0.48 ± 0.26 vs.0.23 ± 0.18, respectively, P=0.002) Also, serum GZM-B levels in the AR group were elevated than those in the functionally stabilized children (120.07 ± 91.42p g/ml and, 60.16 ± 46.29 pg/ml respectively, P=0.01). ROC curve evidenced that measuring FOXP3 mRNA may have a scope as a decision-taking agent in clinical proceedings to diagnose AR. Measuring peripheral blood FOXP3 mRNA elucidated scope to help in the noninvasive diagnosis of AR. Conclusions: Our results emphasize FOXP3 mRNA as a biomarker for AR in pediatrics. Assessment of regulatory/cytotoxic profiles in the peripheral blood of pediatric renal transplant recipients is a potentially useful tool for patient selection and early detection of rejection. Depending on many variables, such as the method of sample normalization, the technique used, the extent of graft inflammation, the immunosuppression regimen, depletion/ repletion of T-lymphocyte component, the importance of FOXP3 may differ.
急性排斥反应的儿童肾移植受者血液中的调节性/细胞毒性T细胞谱
背景:调节细胞和细胞毒性细胞之间的平衡可能决定移植物的后果。我们研究了儿童肾移植受者外周血中主要调节和细胞毒性标志物(即FOXP3和颗粒酶B (GZM-B))的表达与急性排斥反应(AR)的关系。方法:回顾性分析47例儿童首次肾移植受者外周血FOXP3 mRNA表达及血清GZM-B水平,其中17例患儿为AR;而其余30名儿童的同种异体移植物功能稳定。结果:AR组患儿FOXP3 mRNA水平与GADPH mRNA (FOXP3 mRNA/GADPH mRNA)表达水平显著高于同种异体肾移植稳定组(分别为0.48±0.26 vs.0.23±0.18,P=0.002), AR组血清GZM-B水平显著高于功能稳定组(分别为120.07±91.42 g/ml和60.16±46.29 pg/ml, P=0.01)。ROC曲线证明,检测FOXP3 mRNA可能在临床诊断AR过程中具有决策作用。检测外周血FOXP3 mRNA阐明了有助于AR无创诊断的范围。结论:我们的研究结果强调FOXP3 mRNA作为儿科AR的生物标志物。评估儿童肾移植受者外周血中的调节/细胞毒性谱是患者选择和早期发现排斥反应的潜在有用工具。根据许多变量,如样本归一化方法、使用的技术、移植物炎症程度、免疫抑制方案、t淋巴细胞成分的消耗/补充,FOXP3的重要性可能有所不同。
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