TLR‐2, TLR‐4 and MyD88 genes expression in renal transplant acute and chronic rejections

Abstract

Background Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll‐like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. Methods In present research, we have evaluated the mRNA expressions of TLR‐4, TLR‐2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T‐cell‐mediated rejection (ACMR), six acute antibody‐mediated rejection (AAMR), 10 chronic T‐cell‐mediated rejection (CCMR) and four chronic antibody‐mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real‐time polymerase chain reaction (RT‐PCR). Results It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. Conclusion These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell‐mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

“…Increased messenger RNA expression of TLR2 in the cardiac allograft is associated with increased risk of cardiac allograft rejection in humans ( 141 ). This is in line with earlier studies showing similar findings in kidney transplantation ( 143 , 144 ). A recent study using TLR2-deficient mice on the other hand showed poor graft survival time, due to increased immune cell infiltration and enhanced pro-inflammatory Th17 cell responses ( 148 ).…”

“…There is strong evidence that TLR4 contributes to IRI in both MI (138)(139)(140) and HTx (137,141). The role of TLR4 in transplantation has also been confirmed for other solid organ transplants (142)(143)(144)(145). Given these observations, TLR4 inhibition may have beneficial effects in limiting IRI.…”

Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation

“…Our group characterized the molecular signature of PBMCs and CD4+ T lymphocytes isolated from patients with chronic antibody-mediated rejection, demonstrating the specific activation of interferon alpha signaling [8]. Sharbafi et al reported that increased gene expression of toll-like receptor 4 (TLR4) in PBMCs could be suggestive of cell-mediated rejections [9]. Danger et al described that miR-142-5p in circulating immune cells might represent a useful as a biomarker in antibody-mediated rejection [10].…”

The innate immune system in human kidney inflammaging

“…Glomerular TLR4 expression was also associated with the severity of renal injury [37]. MyD88 gene upregulation in renal tissue and increased levels of TLR4 mRNA in peripheral blood mononuclear cells (PBMCs) have been reported as being suggestive of cell-mediated rejection [38] or graft dysfunction in kidney transplantation [39]. TLR2 and TLR4 have been identified as proinflammatory and fibrotic receptors in peritoneal dialysis (PD), after microbial-and sterile inflammationinduced responses [40].…”