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

• Main Authors: Kevin Budding, Jessica van Setten, Eduard A. van de Graaf, Oliver A. van Rossum, Tineke Kardol-Hoefnagel, Erik-Jan D. Oudijk, C. Erik Hack, Henderikus G. Otten
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-09-01
• Series: Frontiers in Immunology
• Subjects: lung transplantation; thymus and activation-regulated chemokine; chronic lung allograft dysfunction; bronchiolitis obliterans syndrome; chronic rejection
• Online Access: http://journal.frontiersin.org/article/10.3389/fimmu.2017.01109/full

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.