1. The role of IL-23/IL-17 axis in human kidney allograft rejection.
- Author
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Haouami Y, Dhaouadi T, Sfar I, Bacha M, Gargah T, Bardi R, Abderrahim E, Goucha R, Ben Abdallah T, and Gorgi Y
- Subjects
- Acute Disease, Adult, Area Under Curve, Female, Follow-Up Studies, Genotype, Graft Rejection genetics, Graft Rejection prevention & control, Graft Survival genetics, Humans, Immunosuppressive Agents therapeutic use, Interleukin-17 blood, Interleukin-17 genetics, Male, Middle Aged, Postoperative Period, RNA, Messenger biosynthesis, ROC Curve, Receptors, Interleukin blood, Receptors, Interleukin genetics, Retrospective Studies, Young Adult, Graft Rejection physiopathology, Interleukin-17 physiology, Kidney Transplantation, Polymorphism, Single Nucleotide, Receptors, Interleukin physiology
- Abstract
Th17 cell subset has been implicated in autoimmune diseases, tumor immunity and, transplant rejection. In order to investigate the role of IL-17/IL-23 pathway in allograft outcome, intragraft expression of IL-17 mRNA and single nucleotide polymorphisms (SNPs) of IL-17A, IL-17F, IL-17RC, and IL23R genes were evaluated with a quantification of IL-17A, IL-17F, and IL-23 plasma levels. This study revealed that recipients with acute rejection (AR) had a significant increase in IL-17A mRNA expression levels after transplantation compared to controls (P = 0.037). Moreover, IL-17A plasma levels were significantly higher in AR group; pretransplantation (Day-1 [D-1]): P = 0.00022 and posttransplantation (Day 7 [D7]): P < 10
-14 . IL-17F and IL-23 plasma levels were significantly higher in AR at D7 only (47.86 vs. 22.99 pg/ml; and 33.82 vs. 18.811 pg/ml; P = 0.015 and P < 10-17 , respectively). Using receiver-operating characteristic curves, D7 IL-17A and IL-23 plasma levels exhibited excellent sensitivities and specificities for predicting AR. Genetic study revealed no association between IL-17A, IL-17F, IL-17RC, and IL23R studied SNPs and AR. Nevertheless, a significant improvement of graft survival was found in kidney transplant recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G, and *G/A genotypes. Besides, IL-17A mRNA levels were significantly higher in patients carrying the IL-23R*G/G genotype comparatively to those with *G/A genotype. Based on these findings, significant increase of IL-17A mRNA and protein levels in AR recipients that are genetically controlled highlights the role of this cytokine that can be a useful clinical biomarker to predict early acute renal allograft rejection., (©2018 Society for Leukocyte Biology.)- Published
- 2018
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