Cytokine and cytotoxic molecule gene expression determined in peripheral blood mononuclear cells in the diagnosis of acute renal rejection
Cytokine and cytotoxic molecule gene expression determined in peripheral blood mononuclear cells in the diagnosis of acute renal rejection
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DOI：
10.1097/00007890-200010150-00014
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发表时间：
2000-10-15
期刊：
影响因子：
6.2
通讯作者：
Roy, R
中科院分区：
文献类型：
--
作者：
Dugré, FJ;Gaudreau, S;Roy, R
背景预防急性排斥反应是用于降低慢性同种异体移植物排斥反应的长期风险的最普遍措施。到目前为止，活检是监测同种异体移植物急性排斥反应的唯一有用的诊断工具，但这种方法的侵入性限制了它的使用。本研究的目的是探讨外周血免疫标志物作为肾移植急性排斥反应的预测性诊断工具。在研究的61例患者中，13例未发生排斥反应，8例经证实为急性排斥反应，40例因移植物功能障碍而被排除。使用半定量逆转录酶-聚合酶链反应（RT-PCR）检测丝裂原诱导的外周血单核细胞的白细胞介素-（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，其中如果患者的样本的差异表达值等于或高于从非排斥患者计算的平均差异表达值，则认为患者的样本是阳性的。IL-4、IL-5、IL-6、干扰素-γ、穿孔素和颗粒酶B mRNA水平与急性排斥反应相关。当这些细胞因子标志物中至少有两个在一个给定的患者中上调时，75%的排斥受体被确定为对15%的非排斥患者。我们已经发现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价证明是有用的急性排斥移植受体的临床识别和在组织学诊断确认之前的伴随抗排斥治疗的理由。
Background. 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.Methods. 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.Results. 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.Conclusions. 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.