期刊
JOURNAL OF HEART AND LUNG TRANSPLANTATION
卷 32, 期 12, 页码 1233-1240出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2013.09.008
关键词
lung transplantation; genetics; IL-17; chronic rejection; neutrophils
资金
- Glaxo Smith Kline (Belgium) for the Chair in Respiratory Pharmacology at the Katholieke Universiteit Leuven
- Research Foundation Flanders (FWO) [G.0723.10, G.0753.10, G.0679.12, G.0705.12]
- Katholieke Universiteit Leuven [OT10/050]
BACKGROUND: Chronic rejection is the major cause of morbidity and mortality after lung transplantation. Interleukin (IL)-17-producing cells, inducers of airway neutrophilia, play a prominent role in chronic rejection. METHODS: We investigated the association between genetic variants in the lL-17/IL-23 pathway and outcome after lung transplantation. Six genetic variants in IL-17 and IL-23 receptor genes were genotyped in 497 lung transplant patients. Associations with chronic rejection, death, airway and systemic inflammatory parameters were assessed. RESULTS: The rs879574A genetic variant in the IL-17A receptor gene was associated with chronic rejection. In particular, carriers of the rs879574 at-risk A allele exhibited increased susceptibility to chronic rejection, with multivariable-adjusted hazard ratio of 1.47 (95% confidence interval, 1.07-2.03; p = 0.004), but no association was found with death (95% confidence interval, 0.71-1.41; p = 0.14). The prevalence of acute rejection was also higher in the at-risk population (p = 0.001). Interestingly, rs879574A was associated with airway neutrophilia (p = 0.020), suggesting that this variant may functionally affect the IL-17A receptor gene and thereby contribute to chronic rejection after lung transplantation. CONCLUSION: The rs879574A genetic variant is associated with chronic rejection after lung transplantation and is functionally associated with airway neutrophilia. Pre-transplant determination of this genetic variant may improve treatment and follow-up of our patients, aiming to reduce acute and chronic rejection. (C) 2013 International Society for Heart and Lung Transplantation. All rights reserved.
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