Dataset Information

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

ABSTRACT: 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 NF?B 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.

SUBMITTER: Budding K

PROVIDER: S-EPMC5592199 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

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

Budding Kevin K van Setten Jessica J van de Graaf Eduard A EA van Rossum Oliver A OA Kardol-Hoefnagel Tineke T Oudijk Erik-Jan D ED Hack C Erik CE Otten Henderikus G HG

Frontiers in immunology 20170906

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 <i>TARC/CCL17</i> promotor polymorphisms correlate with serum TARC/CCL17 levels, we investigated seven single-nucleotide polymorphisms (SNPs) within this region and their po ...[more]

PMID: 28932229

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Project description:Background:There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics and allograft-specific clinical features at the time of organ offer and investigated whether these variables differed in HCV-viremic versus HCV-negative donors and impacted recipient outcomes. Methods:We conducted a single-center, retrospective cohort study of adult patients who underwent a lung transplant at Brigham and Women's Hospital between March 2017 and October 2018. Patients were stratified based on their donor HCV status (HCV-viremic versus HCV-negative). Donor and allograft-specific characteristics and clinical features including chest imaging and bronchoscopy reports, respiratory cultures, and the donor's oxygenation as measured by the arterial partial pressure of oxygen (PaO2) were collected as well as recipient baseline characteristics and transplant outcomes. Results:During the study period, 42 and 57 lung transplants were performed from HCV-viremic and HCV-negative donors, respectively. Donor age was similar in both cohorts. More HCV-viremic donors died from drug intoxication (71% versus 19%, P=0.0001) and had a history of cigarette use (83% versus 5%, P=0.0001) and drug use (76% versus 49%, P=0.007). There were differences in the baseline recipient characteristics including a lower median lung allocation score in the HCV-viremic cohort. The organ-specific clinical characteristics including the terminal PaO2, chest imaging and bronchoscopy findings, and evidence of pulmonary infection were similar between the two cohorts. The recipient outcomes overall were excellent and did not differ significantly in both cohorts in terms of graft and patient survival at 6 and 12 months. Conclusions:Despite a greater proportion of HCV-viremic donors being increased risk with a history of drug and cigarette use and having died as a result of drug intoxication, the quality of the HCV-viremic donor organs did not differ from the HCV-negative donor organs or impact graft and recipient survival. Due to an increasing number of transplants from increased risk donors and in order to develop safe and effective protocols to perform lung transplants from HCV-infected donors, further characterization of the donor and allograft-specific clinical features and longer-term recipient outcomes is greatly needed.

Dataset Information

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

Publications

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

Similar Datasets

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