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白介素-17A、白介素-17RC 多态性与白介素-17 血浆水平在突尼斯类风湿关节炎患者中的研究。

IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis.

机构信息

Research Laboratory in Immunology of Renal Transplantation and Immunopathology (LR03SP01), Charles Nicolle Hospital, Tunis, Tunisia.

Department of Rheumatology, Charles Nicolle Hospital, Tunis, Tunisia.

出版信息

PLoS One. 2018 Mar 27;13(3):e0194883. doi: 10.1371/journal.pone.0194883. eCollection 2018.

Abstract

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-17Ars2275913 and IL-17RCrs708567 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-17Ars2275913 (G/A) and IL-17RCrs708567 (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.

摘要

背景

白细胞介素-17(IL-17),一种主要由 Th17 细胞分泌的细胞因子,似乎在类风湿关节炎(RA)的发病机制中发挥重要作用。IL-17 及其受体基因的功能性遗传多态性可以在质量或数量上影响其功能。因此,我们旨在研究 IL17-A 和 IL17RC 多态性对 IL-17 血浆水平和 RA 易感性和严重程度的影响。

方法

在这种情况下,我们研究了 115 例 RA 患者和 91 名年龄、性别和种族相匹配的健康对照者的 IL-17Ars2275913 和 IL-17RCrs708567 多态性,并同时检测了 IL17 血浆水平。

结果

IL-17A 和 IL-17RC 研究多态性与 RA 易感性之间无统计学显著关联。相反,患者的 IL-17A 血浆水平明显高于对照组(55.07pg/ml 对 4.75pg/ml),p<10E-12。ROC 曲线用于评估血浆 IL-17 在检测 RA 中的性能。在特异性为 100%时,IL-17A 的最高灵敏度为 18.25pg/ml 时为 61.7%;p<10E-21,CI=[0.849-0.939]。分析结果表明,与携带G/G 和G/A 基因型的患者相比,IL-17RC*A/A 基因型患者的 IgM-类风湿因子和抗 CCP 抗体明显较少;p=0.013 和 p=0.015。另一方面,IL-17 血浆水平分析显示与 RA 的活动度显著相关(DAS28≥5.1=74.71pg/ml 与 DAS28<5.1=11.96pg/ml),p<10E-6。

结论

IL-17Ars2275913(G/A)和 IL-17RCrs708567(G/A)多态性似乎不影响突尼斯人群的 RA 易感性。这一结果与之前报道的结果一致。IL-17A 血浆水平似乎可预测严重 RA 的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2365/5870983/10b582de7bbd/pone.0194883.g001.jpg

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