Sequential monitoring of TIM-3 mRNA expression in blood and urine samples of renal transplant recipients

Abstract

Background: T cell immunoglobulin and mucin domain 3 (TIM-3), as a co-inhibitory receptor expressed on Th1, Th17, CD8T, FoxP3 + Treg and innate immune cells, plays an important role in suppression of T cell-mediated immune responses, tolerance induction and T cell exhaustion. In this study, we evaluated sequential alterations of TIM-3 mRNA expression level in blood and urine samples of renal transplant recipients to predict approaching clinical episodes.

Methods: A total of 52 adult renal transplant recipients (31 male and 21 female) were enrolled in this study. All the patients received kidney transplant from living unrelated donors. TIM-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and urinary cells were quantified using Real Time TaqMan polymerase chain reaction (PCR) at 4 different time points (pre-transplantation, 2, 90 and 180 days post-transplantation).

Result: TIM-3 mRNA expression level on days 2, 90 and 180 after transplantation was significantly higher in blood and urine samples of patients with graft dysfunction (GD) compared with patients with well-functioning graft (WFG). Our results also showed a high correlation between blood and urinary level of TIM-3 mRNA expression. The data from Receiver Operating Characteristic (ROC) Curve Analysis showed that blood and urinary TIM-3 mRNA expression level at month 3 and 6 could discriminate graft dysfunction (GD) from well-functioning graft (WFG) with high specificity and sensitivity.

Conclusion: Our data suggested that serial monitoring of TIM-3 mRNA level in the blood and urine samples of renal transplant recipients could be a useful non-invasive biomarker for prediction and diagnosis of allograft dysfunction.

Keywords: Graft dysfunction; Renal transplantation; TIM-3.