The role of IL-23/IL-17 axis in human kidney allograft rejection

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Youssra Haouami¹  Tarak Dhaouadi¹  Imen Sfar¹  Mongi Bacha¹  Tahar Gargah¹  Rafika Bardi¹  Ezzeddine Abderrahim¹  Rym Goucha¹  Taïeb Ben Abdallah¹  Yousr Gorgi¹ 

[1] Research Laboratory in Immunology of Renal Transplantation and Immunopathology (LR03SP01), Charles Nicolle Hospital, Tunis El Manar University;Department of Nephrology and Internal Medicine, Charles Nicolle Hospital;Department of Pediatric nephrology, Charles Nicolle Hospital

关键词: acute rejection;    mRNA;    plasma level;    SNPs;    Th17;    transplantation;   

DOI  :  10.1002/JLB.5AB0318-148R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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, IL17RC, 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.

【 授权许可】

CC BY