Guanylate-binding protein 2 mRNA in peripheral blood leukocytes of liver transplant recipients as a marker for acute cellular rejection

Abstract

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.