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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. [ABSTRACT FROM AUTHOR]

Background: Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. Methods: In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. Results: There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849–0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels’ analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. Conclusion: IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence. [ABSTRACT FROM AUTHOR]