TLR2 and TLR4 mRNA expression levels in liver transplant patients with acute rejection

Abstract

Toll-like receptors (TLRs) have important role in transplant outcomes by activating the innate immune system and production of pro-inflammatory cytokines, leading to graft rejection. We assessed the expression level of TL2 and TLR4 in acute rejection (AR) on the 1st and 7th^-day post-transplantation. TLR2 and TLR4 expressions were evaluated by real-time PCR in both the AR group (n = 50) and non-AR (n = 50), compared with the control group. Also, the correlation of the expression levels of TLRs between both the 1st and 7th day was analyzed. ROC curve analysis was used to determine the cut-off value for TLRs expression. TLR4 mRNA expression was significantly up-regulated in AR patients vs. the controls on the 1st day (p ≤ 0.05) and it was down-regulated in non-AR vs. controls on the 1st day (p ≤ 0.05). Also, TLR4 expression had decreased in both AR and non-AR groups vs. control on the 7th day (p ≤ 0.05). Both TLR2 and TLR4 expression in comparison to non-AR had increased in the AR group on the 7th day (p ≤ 0.05). TLR2 expression positively correlated between 1st and 7th day in AR (r = 0.3, (p ≤ 0.05) and non-AR group (r = 0.2, p ≤ 0.05). ROC curve analysis showed a cut-off value of TLR2 up to 0.98 with sensitivity 71.05 (95%CI = 54.1-84.6) and specificity 63.27 (95%CI = 48.3-76.6) that could distinguish between AR and non-AR group (p ≤ 0.05). The data support that both TLR2 and TLR4 expression have an effective role in AR after liver transplantation and could be used as possible biomarkers for AR to choose better therapeutic strategies based on immunological aspects.

Keywords: Acute rejection; Liver transplantation; Toll-like receptor.