Dugré F J, Gaudreau S, Belles-Isles M, Houde I, Roy R
Centre de recherche et Immunologie, CHUQ, Université Laval, Québec, Canada.
Transplantation. 2000 Oct 15;70(7):1074-80. doi: 10.1097/00007890-200010150-00014.
Prevention of acute rejection is the most prevalent measure used to reduce the long-term risk of chronic allograft rejection. Until now, biopsy was the only useful diagnostic tool for monitoring allograft acute rejection, but invasiveness of this procedure limits its use. The aim of this study was to investigate the implication of peripheral blood immune markers as a predictive diagnostic tool preceding biopsy in acute renal allograft rejection determination.
Of the 61 patients studied, 13 had no rejection episodes, 8 had a proven acute rejection, and 40 were excluded for graft dysfunction causes. Mitogen-induced peripheral blood mononuclear cells were tested for interleukin- (IL) 2, IL-4, IL-5, IL-6, IL-10, IL-15, Interferon-gamma, Perforin, Granzyme B, and Fas L using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). An up-regulated mRNA expression value was calculated in which a patient's sample was deemed positive if its differential expression value was equal or higher than the mean differential expression value calculated from the nonrejecting patients.
IL-4, IL-5, IL-6, Interferon-gamma, Perforin, and Granzyme B mRNA levels were associated with acute rejection. When at least two of these cytokine markers were up-regulated in a given patient, 75% of the rejecting recipients were identified against 15% of the nonrejecting patients.
We have shown that acute rejection episodes in renal transplant recipients were associated with an increase in mRNA expression of cytokines in mitogen-induced peripheral blood mononuclear cells. The evaluation of pro-inflammatory cytokines and cytotoxic molecules prove useful in the clinical identification of acutely rejecting transplant recipients and in the justification of concomitant antirejection therapy before histological diagnosis confirmation.
预防急性排斥反应是降低慢性移植排斥反应长期风险最常用的措施。到目前为止，活检是监测移植急性排斥反应的唯一有效诊断工具，但该操作的侵入性限制了其应用。本研究的目的是探讨外周血免疫标志物作为预测诊断工具在肾移植急性排斥反应活检前诊断中的意义。
在61例研究患者中，13例无排斥反应，8例确诊为急性排斥反应，40例因移植功能障碍原因被排除。使用半定量逆转录聚合酶链反应（RT-PCR）检测丝裂原诱导的外周血单个核细胞中的白细胞介素-（IL）2、IL-4、IL-5、IL-6、IL-10、IL-15、干扰素-γ、穿孔素、颗粒酶B和Fas L。计算上调的mRNA表达值，如果患者样本的差异表达值等于或高于从无排斥反应患者计算出的平均差异表达值，则该样本被视为阳性。
IL-4、IL-5、IL-6、干扰素-γ、穿孔素和颗粒酶B的mRNA水平与急性排斥反应相关。当给定患者中至少两种这些细胞因子标志物上调时，75%的排斥反应受者被识别出来，而无排斥反应患者中这一比例为15%。
我们已经表明，肾移植受者的急性排斥反应与丝裂原诱导的外周血单个核细胞中细胞因子mRNA表达的增加有关。促炎细胞因子和细胞毒性分子的评估在临床识别急性排斥反应的移植受者以及在组织学诊断确认前进行抗排斥治疗的合理性方面证明是有用的。
