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Published on: May 2, 2013
Toll-like receptor 4 and CD14 gene polymorphisms in Tunisian kidney transplantation
H Krichen1, Y Gorgi, T Dhaouadi
1Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), University Tunis El Manar, Charles Nicolle Hospital, Tunis, Tunisia.
Background:
Acute and chronic rejections remain an important cause of graft loss after renal transplantation. Currently, activation of innate immune responses through Toll-like receptors (TLRs) is suspected to be implied in the loss of the transplant tolerance.
Objectives:
We investigated functional single nucleotide polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation and looked for any potential role in acute rejection (AR) and chronic allograft nephropathy (CAN) and impact on graft survival.
Patients And Methods:
TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 209 kidney transplant recipients (KTRs) including 132 treated with mycophenolate mofetil (MMF+). AR occurred in 59 patients and 24 were identified as having CAN by biopsy and scored according to the Banff criteria.
Results:
There were no significant associations between TLR4 and CD14 genotypes and alleles and the occurrence of both AR episodes and CAN. Moreover, TLR4 and CD14 SNPs did not seem to influence kidney graft survival. Analysis according to human leukocyte antigen (HLA) compatibility status, positivity of anti-HLA antibodies, and immunosuppression by MMF confirmed the absence of correlation of the investigated SNPs with the graft outcome. In addition, incidence of post-transplantation infections, including cytomegalovirus (CMV) infections, was not influenced by both TLR4 and CD14 SNPs.
Conclusion:
These results suggest that TLR4 (Asp299Gly) and CD14 (C/T -159) functional SNPs do not play a major role in AR, CAN, and kidney graft survival. Therefore, intragraft monitoring of TLR4/CD14 genes expression by messenger RNA (mRNA) would provide clarity on the exact role of these receptors in graft injuries.
Insights
Single nucleotide polymorphisms (SNPs) in Toll-like receptor 4 (TLR4) and CD14 do not appear to influence acute rejection, chronic allograft nephropathy, or kidney transplant survival. Further research on gene expression is recommended for clarity.
Area of Science:
- Immunogenetics
- Transplantation Immunology
- Molecular Biology
Background:
- Graft loss after renal transplantation is often due to acute and chronic rejections.
- Toll-like receptors (TLRs) activation is implicated in the loss of transplant tolerance.
Purpose of the Study:
- To investigate the role of functional single nucleotide polymorphisms (SNPs) in TLR4 and its coreceptor CD14 in kidney transplantation.
- To determine the impact of these SNPs on acute rejection (AR), chronic allograft nephropathy (CAN), and kidney graft survival.
Main Methods:
- TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were genotyped in 209 kidney transplant recipients using PCR-RFLP.
- AR and CAN were diagnosed by biopsy and scored using Banff criteria.
Main Results:
- No significant associations were found between TLR4/CD14 genotypes/alleles and the occurrence of AR or CAN.
- TLR4 and CD14 SNPs did not influence kidney graft survival, HLA compatibility, anti-HLA antibodies, or immunosuppression with MMF.
- Incidence of post-transplantation infections, including CMV, was not affected by TLR4/CD14 SNPs.
Conclusions:
- Functional SNPs of TLR4 (Asp299Gly) and CD14 (C/T -159) do not appear to be major factors in AR, CAN, or kidney graft survival.
- Intragraft gene expression analysis of TLR4/CD14 via mRNA is suggested to elucidate their precise role in graft injuries.
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