Krichen H, Gorgi Y, Dhaouadi T, Mecheri Y, Sfar I, Bardi R, Bacha M M, Abderrahim E, Jendoubi-Ayed S, Ayed K, Ben Abdallah T
Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), University Tunis El Manar, Charles Nicolle Hospital, Tunis, Tunisia.
Transplant Proc. 2013;45(10):3472-7. doi: 10.1016/j.transproceed.2013.09.003.
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.
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.
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.
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.
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.
急性和慢性排斥反应仍然是肾移植后移植物丢失的重要原因。目前，怀疑通过Toll样受体（TLR）激活固有免疫反应与移植耐受的丧失有关。
我们研究了肾移植中TLR4及其共受体CD14的功能性单核苷酸多态性（SNP），并寻找其在急性排斥反应（AR）和慢性移植肾肾病（CAN）中的任何潜在作用以及对移植物存活的影响。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测209例肾移植受者（KTR）的TLR4（Asp299Gly）和CD14（C/T -159）SNP，其中132例接受霉酚酸酯治疗（MMF+）。59例患者发生AR，24例经活检确诊为CAN，并根据Banff标准进行评分。
TLR4和CD14的基因型和等位基因与AR发作和CAN的发生之间无显著关联。此外，TLR4和CD14 SNP似乎不影响肾移植存活。根据人类白细胞抗原（HLA）相容性状态、抗HLA抗体阳性以及MMF免疫抑制进行分析，证实所研究的SNP与移植物结局无相关性。此外，包括巨细胞病毒（CMV）感染在内的移植后感染发生率不受TLR4和CD14 SNP的影响。
这些结果表明，TLR4（Asp299Gly）和CD14（C/T -159）功能性SNP在AR、CAN和肾移植存活中不发挥主要作用。因此，通过信使核糖核酸（mRNA）对移植物内TLR4/CD14基因表达进行监测将明确这些受体在移植物损伤中的确切作用。
