Title：Diagnosis of acute renal allograft rejection by analyzing whole blood mRNA
expression of lymphocyte marker molecules.
题目：通过分析全血淋巴细胞标志分子的mRNA表达来诊断急性肾移植排斥。
Author：Alakulppi NS, Kyllonen LE, Partanen J, Salmela KT, Laine JT.
作者：Alakulppi NS, Kyllonen LE, Partanen J, Salmela KT, Laine JT.
Source：Transplantation. 2007 Mar 27;83 :791-8.
来源：Transplantation. 2007 Mar 27;83 :791-8.
Abstract：BACKGROUND: Currently, the diagnosis of acute rejection after kidney transplantation is based on a kidney biopsy taken after clinical rejection suspicion. A robust, noninvasive diagnostic method would allow easier and more frequent monitoring of the patient and the graft. Potentially, a straightforward method would be the analysis of lymphocyte marker molecule expression from whole blood samples. METHODS: Whole blood samples were collected prospectively in a single kidney transplantation center from 50 adult kidney recipients transplanted between 2001 and 2005. The mRNA expression of granzyme B, perforin, FasL, granulysin, CD154, ICOS, CTLA4 and PD-1 were analyzed with real-time quantitative polymerase chain reaction. RESULTS: The expression of ICOS and CD154 were significantly lower in rejection patients than in control patients (P<0.001). Both genes gave statistically significant area under receiver operating characteristic curve (AUC; 0.87, 0.88) with 84% sensitivity and 100% specificity for CD154 and 76% and 86% for ICOS, respectively. In paired rejection and postrejection therapy samples, the expression of both genes significantly increased during rejection therapy (P<0.001). When rejection patients were compared to patients biopsied because of other reasons of graft dysfunction, both CD154 and ICOS were lower in rejection patients but only CD154 was statistically significant (P=0.028, AUC=0.740, sensitivity 52%, specificity 90%). The other studied genes gave no consistent statistically significant results. CONCLUSIONS: The whole blood gene expression quantities of costimulatory molecules CD154 and ICOS reasonably robustly differentiated rejection patients from control patients. The clinical use of the analysis is limited by poor capability to differentiate patients with rejection from patients with other causes of graft dysfunction.
摘要：背景：目前肾移植后的急性排斥的诊断主要依靠临床怀疑排斥后所做的肾脏活检。一个可靠的无创诊断方法将使得对患者和移植肾的监测更简洁，更频繁。分析来自全血样本的淋巴细胞标志分子的表达将有可能成为一种简单易行的方法。方法：前瞻性地取2001年到2005年某肾脏移植中心50名成年肾脏移植患者的全血样本。利用实时定量PCR检测granzyme B ,穿孔素、FasL，granulysin,CD 154,ICOS,CTLA4和PD-1的mRNA的表达。结果：ICOS和CD154的表达在排异患者中明显低于对照患者（P<0.001）。在受者操作特征曲线（AUC；0.87，0.88）下两个基因都统计学意义，CD154有84%敏感性和100%特异性，ICOS分别是76%和86%。在成对的排异和排异后治疗样本中，两个基因在排异治疗中的升高具有统计学意义（P<0.001）。当排异患者和由于其他原因引起移植物功能衰竭的活检患者作比较时，CD154和ICOS在排异患者都很低，但只有CD154具有统计学意义（P=0.028，AUC=0.740，敏感性52%，特异性90%）。其他被研究的基因无持续有统计学意义的结果。结论：共刺激分子CD154和ICOS的全血基因表达量能可靠的区分排异患者和对照患者。因为在区分排异和其他原因引起的移植物功能衰竭方面的能力较差，所以临床应用的受到限制。
编译：Alakulppi NS等在近期发表在《移植》杂志上的研究表明，通过分析全血淋巴细胞标志分子的mRNA表达将可能诊断急性肾移植排斥。他们前瞻性地获取了2001年到2005年某肾脏移植中心50名成年肾脏移植患者的全血样本，对一组基因作了实时定量PCR检测，结果发现ICOS和CD154的表达在排异患者中明显低于对照患者（P<0.001）。在受者操作特征曲线（AUC；0.87，0.88）下两个基因都统计学意义，CD154有84%敏感性和100%特异性，ICOS分别是76%和86%。在成对的排异和排异后治疗样本中，两个基因在排异治疗中的升高具有统计学意义（P<0.001）。当排异患者和由于其他原因引起移植物功能衰竭的活检患者作比较时，CD154和ICOS在排异患者都很低，但只有CD154具有统计学意义（P=0.028，AUC=0.740，敏感性52%，特异性90%）。其他被研究的基因无持续有统计学意义的结果。他们认为共刺激分子CD154和ICOS的全血基因表达量能可靠的区分排异患者和对照患者。因为在区分排异和其他原因引起的移植物功能衰竭方面的能力较差，所以临床应用的受到限制。
