Association between a Single Donor TARC/CCL17 Promotor Polymorphism and Obstructive Chronic Lung Allograft Dysfunction after Lung Transplantation

Frontiers in Immunology

Erik-Jan D. Oudijk¹  Jessica van Setten²  C. Erik Hack³  Eduard A. van de Graaf⁴  Tineke Kardol-Hoefnagel⁶  Henderikus G. Otten⁶  Kevin Budding⁶  Oliver A. van Rossum⁶ 

[1] Center of Interstitial Lung Diseases, St. Antonius Hospital, Nieuwegein, Netherlands;Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands;Department of Dermatology, University Medical Center Utrecht, Utrecht, Netherlands;Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, Netherlands;Department of Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands;Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands;

关键词: lung transplantation;    thymus and activation-regulated chemokine;    chronic lung allograft dysfunction;    bronchiolitis obliterans syndrome;    chronic rejection;   

DOI  :  10.3389/fimmu.2017.01109

来源: DOAJ

【 摘 要 】

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 TARC/CCL17 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 (p = 0.066). Interestingly, this SNP configuration in patients did not show any correlation with pre-LTx TARC/CCL17 serum levels (p = 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 (p = 0.023) and survival rate (p = 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 TARC/CCL17 promotor SNP in the donor correlates with lower serum TARC/CCL17 levels measured 1 month after LTx and affects clinical outcome after LTx.

【 授权许可】

Unknown