Sequential monitoring of TIM-3 gene expression in peripheral blood for diagnostic and prognostic evaluation of acute rejection in renal graft recipients.

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 (r2=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.