Sequential Monitoring of TIM-3 Gene Expression in Peripheral Blood for Diagnostic and Prognostic Evaluation of Acute Rejection in Renal Graft Recipients

Abstract

Background TIM-3 is expressed on primary T effector cells, including th1, ctl, and Th17, which play essential roles in acute allograft rejection (AR). In this study we monitored sequential changes of TIM-3 gene expression among peripheral blood leukocytes (PBL) from renal transplant recipients. Methods The study consisted of an AR group (n = 24), a no AR group (n = 20), and a stable group (n = 18). Prospective serial blood samples were collected after allotransplantation and during AR episodes. The mRNA encoding for TIM-3 was quantified using real-time reverse-transcription polymerase chain reaction (RT-PCR). Statistical analyses were performed to correlate gene transcript measurements with clinical events. Results TIM-3 mRNA in PBL showed significantly higher expression in the AR compared with the no AR and stable groups: 286.72 ± 86.28 vs 126.10 ± 28.31 vs 96.91 ± 17.88, respectively ( P = .00). The receiver operating characteristic curve showed a specificity of 100% and a sensitivity of 87.5% for the utility of TIM-3 for rejection diagnosis. Antirejection therapy decreased TIM-3 mRNA expression in all AR patients. There was a positive correlation between TIM-3 mRNA expression and serum creatinine ( r 2 = 0.716; P = .00). Conclusions TIM-3 mRNA quantification by RT-PCR in PBL may be a promising tool for a noninvasive diagnosis of AR. But the utility for predicting the prognosis of AR after antirejection treatment was limited, owing to the great variations of TIM-3 mRNA expression during AR episodes.