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Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation
Published on: November 7, 2020
TLR2 and TLR4 mRNA expression levels in liver transplant patients with acute rejection
Zahra Keshavarz1, Neda Zareei2, Afsoon Afshari3
1Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran.
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.
Insights
Toll-like receptors (TLRs) play a key role in transplant rejection. This study found that TLR2 and TLR4 expression levels can help identify acute rejection (AR) after liver transplantation, suggesting their potential as biomarkers.
Area of Science:
- Immunology
- Transplantation Science
- Molecular Biology
Background:
- Toll-like receptors (TLRs) are crucial in innate immunity and cytokine production, influencing transplant outcomes.
- Activation of TLRs can lead to graft rejection, highlighting their significance in transplantation.
Purpose of the Study:
- To assess the expression levels of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in acute rejection (AR) post-liver transplantation.
- To determine the correlation of TLR expression between the 1st and 7th day post-transplantation.
- To evaluate the potential of TLR2 and TLR4 as biomarkers for AR.
Main Methods:
- Real-time PCR was used to measure TLR2 and TLR4 mRNA expression in patients with AR (n=50), without AR (n=50), and controls.
- Expression levels were analyzed on the 1st and 7th day post-transplantation.
- Receiver Operating Characteristic (ROC) curve analysis was performed to determine cut-off values for TLR expression.
Main Results:
- TLR4 mRNA was significantly upregulated in AR patients on day 1 but downregulated in non-AR patients compared to controls.
- Both TLR2 and TLR4 expression increased in the AR group compared to the non-AR group on day 7.
- TLR2 expression showed a positive correlation between day 1 and day 7 in both AR and non-AR groups.
- ROC analysis identified a TLR2 cut-off value of 0.98, distinguishing AR from non-AR with 71.05% sensitivity and 63.27% specificity.
Conclusions:
- TLR2 and TLR4 expression are significantly associated with acute rejection following liver transplantation.
- These TLRs demonstrate potential as predictive biomarkers for AR.
- Understanding TLR involvement can guide the development of targeted immunotherapeutic strategies.
