Dhaouadi T, Sfar I, Bardi R, Jendoubi-Ayed S, Abdallah T B, Ayed K, Gorgi Y
Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), University Tunis EI Manar, Charles Nicolle Hospital, Tunis, Tunisia.
Transplant Proc. 2013 Jul-Aug;45(6):2152-7. doi: 10.1016/j.transproceed.2012.12.006. Epub 2013 Jun 6.
Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft.
We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection.
TNF-α (G/A -308), TGF -β1 (haplotype codon 10/codon 25), IL-10 (haplotype-1082, -819, -592), IL-6 (C/G -174), and IFN-γ (T/A +874) single nucleotide polymorphisms (SNPs) were detected using polymerase chain reaction (PCR)-specific sequence primers (SSP) in 231 kidney transplant recipients (KTR) including 106 treated with mycophenolate mofetil (MMF+).
We observed no significant associations of any of investigated polymorphism taken alone with acute rejection episodes (ARE) or chronic allograft dysfunction (CAD). Nevertheless, TGF-β1 Low (L) production was correlated with greater graft survival at 20 years (81.8%) compared with intermediate (L) or high (H) levels (56.1%), affect that the difference was not significant (P = .2). Cytokine haplotype analysis in KTR (MMF-) without HLA-mismatches or presynthesized anti-HLA antibodies (n = 32) showed ARE to be significantly more prevalent among the TNF-αH/TGF- β1H/IL-10*H production haplotype (75%) compared with the other haplotypes (16%; P = .03).
The presence of TGF-β1-H secretion profile may protect the kidney graft. TNF-αH/TGF-β1H/IL-10*H haplotype was associated with a higher risk of ARE and with poorer graft survival.
急性和慢性排斥反应仍是肾移植后移植物丢失的重要原因。有人提出，细胞因子基因分型可能具有预测作用，可识别出无论肾移植前人类白细胞抗原（HLA）相容性和/或抗HLA抗体情况如何，发生排斥反应风险更高的患者。
我们试图研究肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β1、白细胞介素（IL）-10、IL-6和干扰素（IFN）-γ的多态性，作为肾移植中细胞因子产生差异的指标，并检验它们对急性或慢性排斥反应的预测作用。
使用聚合酶链反应（PCR）特异性序列引物（SSP），在231例肾移植受者（KTR）中检测TNF-α（G/A -308）、TGF -β1（单倍型密码子10/密码子25）、IL-10（单倍型-1082、-819、-592）、IL-6（C/G -174）和IFN-γ（T/A +874）单核苷酸多态性（SNP），其中106例接受霉酚酸酯治疗（MMF+）。
我们观察到，单独研究的任何一种多态性与急性排斥反应发作（ARE）或慢性移植物功能障碍（CAD）均无显著关联。然而，与中等（L）或高（H）水平（56.1%）相比，TGF-β1低（L）分泌水平与20年时更高的移植物存活率（81.8%）相关，尽管差异不显著（P = 0.2）。在无HLA错配或预合成抗HLA抗体的KTR（MMF-）（n = 32）中进行的细胞因子单倍型分析显示，与其他单倍型（16%；P = 0.03）相比，TNF-αH/TGF- β1H/IL-10*H产生单倍型中ARE明显更普遍（75%）。
TGF-β1-H分泌谱的存在可能对肾移植物起到保护作用。TNF-αH/TGF-β1H/IL-10*H单倍型与更高的ARE风险及更差的移植物存活率相关。
