Increased Expression of Toll-Like Receptors 2 and 4 in Renal Transplant Recipients that Develop Allograft Dysfunction: A Cohort Study

Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells (PBMCs) can predict the clinical outcome of kidney allografts. Methods: We obtained blood samples from 52 renal transplant patients before transplant, and 2, 90, and 180 days post-transplantation in order to analyze the surface expressions of TLR-2 and TLR-4 on peripheral blood monocytes. The expression patterns of TLR-2 and TLR-4 were compared between patients with graft dysfunction (GD) and those with well-functioning graft (WFG). Results: Significantly different mean dynamic changes in surface expression of TLR-2, according to percentage of TLR-2+ cells, between (the GD and WFG) groups existed at most time-points before and after renal transplantation (p=0.007) with the exception of  day 2 post-transplantation. We observed significantly higher mean fluorescence intensities of TLR-2 and TLR-4 on CD14+ cells in the GD group compared to the WFG group. This finding was particularly observed 180 days post-transplantation (p=0.001). Based on TLR-2 and TLR-4 protein expression for each step, multiple logistic regression and ROC curve analysis revealed that an increase in CD14+ TLR-2+ monocytes within the 90 days  post-transplantaton was associated with increased risk of GD at 180 and 365 days post-transplantation  [odds ratio (OR)=1.27, p=0.005)]. Conclusion: Sequential monitoring of TLR-2 and TLR-4 expression patterns in peripheral blood monocytes appear to be prognostic and predictive biomarkers for early and late kidney allograft outcomes.