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.