The role of IL-23/IL-17 axis in human kidney allograft rejection. Issue 6 (19th July 2018)

• Record Type: Journal Article
• Authors: Haouami, Youssra; Dhaouadi, Tarak; Sfar, Imen; Bacha, Mongi; Gargah, Tahar; Bardi, Rafika; Abderrahim, Ezzeddine; Goucha, Rym; Ben Abdallah, Taïeb; Gorgi, Yousr
• Is Part Of: Journal of leukocyte biology. Volume 104:Issue 6(2018)
• Page Start: 1229
• Page End: 1239
• Publication Date: 2018-07-19
• Subjects: acute rejection -- mRNA -- plasma level -- SNPs -- Th17 -- transplantation; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.5AB0318-148R
• Languages: English
• ISSNs: 0741-5400

Abstract

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. Study showing significant associations between Day 7 plasma IL-17A, IL-17F and IL-23 and AR with good performances for IL-17A and IL-23 in predicting acute rejection (AR) occurrence; significant increase of IL-17A expression in kidney graft in case of AR; a significant improvement of graft survival in recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G and *G/A genotypes.