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细胞因子和趋化因子是否适合作为 Takayasu 动脉炎的生物标志物?

Are cytokines and chemokines suitable biomarkers for Takayasu arteritis?

机构信息

Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, Rua Botucatu, 740, 3rd Floor, São Paulo, SP zip code: 04032-900, Brazil.

Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.

出版信息

Autoimmun Rev. 2017 Oct;16(10):1071-1078. doi: 10.1016/j.autrev.2017.07.023. Epub 2017 Aug 2.

Abstract

There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.

摘要

在 Takayasu 动脉炎(TA)中,对疾病相关生物标志物的需求日益增长。评估 TA 中的促炎细胞因子和趋化因子可能有助于更好地了解其病理生理学,并且这些介质的循环水平可能作为疾病活动的生物标志物。白细胞介素 6(IL-6)血清水平是 TA 的一个潜在生物标志物,其与 TA 状态和疾病活动密切相关。TA 与血清/血浆中其他细胞因子水平之间的关联则不太明确。TA 患者外周血单核细胞(PBMC)中 IL-4 和肿瘤坏死因子 α(TNFα)的 mRNA 表达持续增加,体外 PBMC 刺激后这两种细胞因子的表达增加更多,而 IL-10 mRNA 的表达减少。此外,TA 患者的循环 T 细胞在体外刺激下产生更高水平的 Th1 和 Th17 相关细胞因子。在 TA 患者的主动脉中,已描述干扰素 γ(IFNγ)、IL-6、IL-12 和 IL-17 的表达增加。关于 TA 中的循环趋化因子,与健康对照组相比,TA 患者的血清/血浆中 IL-8(CXCL8)、CCL2 和 CCL5 水平升高,并且活动期 TA 患者比缓解期患者升高更为明显。血清 IL-6 似乎是 TA 疾病状态和疾病活动的最佳生物标志物,而 Th1 和 Th17 反应的增加在 TA 的病理生理学中占主导地位。

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