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 IL-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.
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 IL-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.
Authors: Tinne Goos; Stijn E Verleden; Laurens J De Sadeleer; Anke Van Herck; Annelore Sacreas; Arno Vanstapel; Janne Kaes; Vincent Geudens; Celine Aelbrecht; David Ruttens; Diether Lambrechts; Sascha Vermeer; Laurens J Ceulemans; Dirk E Van Raemdonck; Laurent Godinas; Jonas Yserbyt; Bart M Vanaudenaerde; Geert M Verleden; Robin Vos; Wim A Wuyts Journal: Transpl Int Date: 2022-05-16 Impact factor: 3.842
Authors: Davide Scozzi; Mohsen Ibrahim; Cecilia Menna; Alexander S Krupnick; Daniel Kreisel; Andrew E Gelman Journal: Am J Transplant Date: 2016-07-25 Impact factor: 8.086