Interleukin-17 receptor polymorphism predisposes to primary graft dysfunction after lung transplantation.
BACKGROUND
Primary graft dysfunction (PGD), with an incidence of 11% to 57%, is a major cause of morbidity and mortality within the first 30 days after lung transplantation (LTx). In this study, we postulate that recipient genetic variants in interleukin-17 and -23 receptor genes (IL-17R and IL-23R, respectively) may predispose LTx recipients to an increased risk for developing PGD.


METHODS
Seven genetic variants of IL-17R and IL-23R were successfully genotyped in 431 lung transplant recipients. Our primary end-point was PGD and secondary end-points were time to extubation, intensive care unit (ICU) stay, bronchoalveolar lavage neutrophilia and serum C-reactive protein.


RESULTS
The AA genotype of the rs882643 genetic variant of IL-17R was associated with higher PGD grades at 0 hour (adjusted p = 0.042), 12 hours (adjusted p = 0.013) and 48 hours (adjusted p = 0.0092) after LTx. The GG genotype of the rs2241049 genetic variant of IL-17R was associated with higher PGD grades at 48 hours (adjusted p = 0.0067) after LTx. For both genetic variants, no association was found with extubation time, ICU stay, post-operative BAL neutrophilia, serum CRP, chronic lung allograft dysfunction (CLAD) or graft loss.


CONCLUSIONS
Both genetic variants of IL-17R (rs882643 and rs2241049) were associated with PGD. This confirms a genetic predisposition toward PGD and suggests a role of IL-17 in driving neutrophilia in PGD.
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Jana
J
Somers
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
David
D
Ruttens
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Stijn E
SE
Verleden
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Elly
E
Vandermeulen
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Davide
D
Piloni
Laboratory of Translational Genetics, Vesalius Research Center; Vesalius Reseach Centrum, VIB, Vlaams Instituut voor Biotechnologie, KU Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
Els
E
Wauters
Laboratory of Translational Genetics, Vesalius Research Center; Vesalius Reseach Centrum, VIB, Vlaams Instituut voor Biotechnologie, KU Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
Diether
D
Lambrechts
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Robin
R
Vos
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Geert M
GM
Verleden
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine.
Bart
B
Vanaudenaerde
Laboratory of Respiratory Disease and Laboratory for Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine. Electronic address: dirk.vanraemdonck@uzleuven.be.
Dirk E
DE
van Raemdonck
D000328:Adult; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D016027:Heart Transplantation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055031:Primary Graft Dysfunction / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate / Q000639:trends
C109985:IL17RA protein, human; D053722:Receptors, Interleukin-17; D004247:DNA
genetics; interleukin-17 receptor; lung transplantation; neutrophils; primary graft dysfunction