Guanylate-binding protein 2 mRNA in peripheral blood leukocytes of liver transplant recipients as a marker for acute cellular rejection
Guanylate-binding protein 2 mRNA in peripheral blood leukocytes of liver transplant recipients as a marker for acute cellular rejection
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DOI：
10.1111/j.1432-2277.2009.00991.x
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发表时间：
2010-04-01
影响因子：
3.1
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Kobayashi, Shogo;Nagano, Hiroaki;Mori, Masaki
在此之前，我们报道了急性细胞排斥反应（ACR）时大鼠外周血中鸟苷酸结合蛋白2（GBP 2）和干扰素调节因子1（IRF 1）的升高，这两个基因是从肝移植的转录组分析中鉴定的，是肝脏中的白细胞相关基因。在这项研究中，我们调查了这两个基因是否可以区分ACR从其他类型的肝功能障碍（LD）的临床。通过实时PCR分析了19例ACR患者和27例LD患者的白细胞以及12例ACR患者和12例LD患者的肝活检组织中的mRNA，以检测GBP 2和IRF 1的表达。使用受试者操作特征（ROC）曲线计算灵敏度和特异性。ACR组鸟苷酸结合蛋白2（GBP 2）和干扰素调节因子1（IRF 1）基因表达水平高于对照组，血液中GBP 2表达水平高于LD组（26.4 ± 3.1和15.6 ± 1.9，P = 0.0203）。多因素分析显示GBP 2/GAPDH比值与ACR相关因素无关（OR = 0.911，P = 0.035）。GBP 2在ACR中的表达水平也高于有丙型肝炎或无LD的肝移植患者。以临界值20为界，基于ROC曲线分析的GBP 2/GAPDH的敏感性和特异性分别为63%和85%。LD患者血清中GBP 2的表达可能有助于ACR的诊断。
P>Previously, we reported guanylate-binding protein 2 (GBP2) and interferon regulatory factor 1 (IRF1) elevated in the rat peripheral blood during acute cellular rejection (ACR), which are identified from transcriptome analysis of liver graft, as leukocyte-related gene in liver. In this study, we investigated whether these two genes could differentially diagnose ACR from other types of liver dysfunction (LD) clinically. The mRNAs from leukocytes of 19 patients with ACR and 27 with LD, as well as from liver biopsies of 12 patients with ACR and 12 with LD, were analysed by real-time PCR for GBP2 and IRF1 expression. Sensitivity and specificity were calculated using receiver operator characteristic (ROC) curves. Guanylate-binding protein 2 (GBP2) and interferon regulatory factor 1 (IRF1) gene expression levels in ACR samples were higher than that in controls, and GBP2 expression in blood was higher than that in LD (26.4 +/- 3.1 and 15.6 +/- 1.9, P = 0.0203). Multivariate analysis showed that the ratio GBP2/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was independent of ACR-related factors (OR = 0.911, P = 0.035). GBP2 expression levels in ACR were also higher than that in liver transplantation patients with hepatitis C or no LD. Using a cut-off value of 20, the sensitivity and specificity of GBP2/GAPDH based on ROC curve analysis were 63% and 85% respectively. GBP2 in the patients with LD may be useful for diagnosis of ACR.