Budding Kevin, van Setten Jessica, van de Graaf Eduard A, van Rossum Oliver A, Kardol-Hoefnagel Tineke, Oudijk Erik-Jan D, Hack C Erik, Otten Henderikus G
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
Front Immunol. 2017 Sep 6;8:1109. doi: 10.3389/fimmu.2017.01109. eCollection 2017.
Lung transplantation (LTx) outcome is hampered by development of chronic rejection, often manifested as the bronchiolitis obliterans syndrome (BOS). Low serum levels of thymus and activation-regulated chemokine (TARC/CCL17), a chemoattractant, measured during the first month post-LTx are predictive for BOS development. Since promotor polymorphisms correlate with serum TARC/CCL17 levels, we investigated seven single-nucleotide polymorphisms (SNPs) within this region and their potential association with LTx outcome. We analyzed donor and patient SNP configurations and haplotypes and observed a trend between a donor SNP (rs223899) configuration and patient TARC/CCL17 serum levels post-LTx ( = 0.066). Interestingly, this SNP configuration in patients did not show any correlation with pre-LTx TARC/CCL17 serum levels ( = 0.776). Survival analysis showed that receiving a graft from a donor heterozygous for rs223899 has a disadvantageous impact on transplantation outcome. When stratified per donor SNP genotype, patients receiving a transplant from a heterozygous donor showed a lower BOS-free survival ( = 0.023) and survival rate ( = 0.0079). Since rs223899 is located within a NFκB binding site, heterozygosity at this position could result in a reduced TARC/CCL17 expression. Our data indicate that a single promotor SNP in the donor correlates with lower serum TARC/CCL17 levels measured 1 month after LTx and affects clinical outcome after LTx.
肺移植（LTx）的结果受到慢性排斥反应发展的阻碍，慢性排斥反应通常表现为闭塞性细支气管炎综合征（BOS）。在LTx术后第一个月测得的低血清水平的胸腺和活化调节趋化因子（TARC/CCL17，一种趋化因子）可预测BOS的发展。由于启动子多态性与血清TARC/CCL17水平相关，我们研究了该区域内的七个单核苷酸多态性（SNP）及其与LTx结果的潜在关联。我们分析了供体和患者的SNP构型及单倍型，观察到一种供体SNP（rs223899）构型与LTx术后患者TARC/CCL17血清水平之间的趋势（P = 0.066）。有趣的是，患者的这种SNP构型与LTx术前TARC/CCL17血清水平无任何相关性（P = 0.776）。生存分析表明，接受来自rs223899杂合供体的移植物对移植结果有不利影响。当按供体SNP基因型分层时，接受杂合供体移植的患者无BOS生存率较低（P = 0.023），生存率也较低（P = 0.0079）。由于rs223899位于一个NFκB结合位点内，该位置的杂合性可能导致TARC/CCL17表达降低。我们的数据表明，供体中的单个启动子SNP与LTx术后1个月测得的较低血清TARC/CCL17水平相关，并影响LTx后的临床结果。
