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成人斯蒂尔病活动期患者循环自然杀伤细胞的特征及其干扰素-γ的产生。

Characteristics of Circulating Natural Killer Cells and Their Interferon-γ Production in Active Adult-onset Still Disease.

机构信息

From the Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine; the Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan.

Y. Shimojima, MD, PhD, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine; D. Kishida, MD, PhD, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine; K.I. Ueno, MD, PhD, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine; S. Ushiyama, MD, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine; T. Ichikawa, MD, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine; Y. Sekijima, MD, PhD, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine and Institute for Biomedical Sciences, Shinshu University.

出版信息

J Rheumatol. 2019 Oct;46(10):1268-1276. doi: 10.3899/jrheum.181192. Epub 2019 Feb 15.

Abstract

OBJECTIVE

To investigate the characteristics of circulating natural killer (NK) cells and their interferon (IFN)-γ-producing ability in adult-onset Still disease (AOSD).

METHODS

Peripheral blood mononuclear cells were obtained from 22 patients in the acute phase of AOSD (acute AOSD); 7 of the 22 patients after treatment (remission AOSD), and 11 healthy controls (HC). NK cells and their IFN-γ expression levels were analyzed by flow cytometry. Additionally, the cytokine receptors of interleukin (IL)-12, IL-15, and IL-18 on NK cells were also evaluated.

RESULTS

The frequency of NK cells was significantly lower in acute AOSD than in HC. NK cell counts significantly increased in remission AOSD. Expression of IL-12 and IL-15 receptors on NK cells was significantly increased in acute AOSD, whereas that of IL-18 receptor indicated no significant difference among 3 groups. IFN-γ expression in NK cells was significantly higher in acute AOSD than in HC, and significantly decreased in remission AOSD. The absolute number of NK cells and IFN-γ-expressing NK cells revealed an inverse correlation with serum ferritin levels in acute AOSD. In 2 distinct subsets of NK cells, CD56 NK cells significantly exhibited higher IFN-γ expression than CD56 NK cells in acute AOSD.

CONCLUSION

In acute AOSD, NK cells displayed lower proportion, whereas they had higher ability for IFN-γ production than in HC; moreover, upregulation of IL-12 and IL-15 receptors on NK cells may promote IFN-γ production. In addition, disease activity may be implicated in regulating the number of NK cells and IFN-γ-expressing NK cells in AOSD.

摘要

目的

探讨成人Still 病(AOSD)患者外周血自然杀伤(NK)细胞的特征及其产生干扰素(IFN)-γ的能力。

方法

采集 22 例 AOSD 急性发作期(急性 AOSD)患者、22 例经治疗缓解后的患者(缓解 AOSD)及 11 例健康对照者(HC)外周血单个核细胞,采用流式细胞术分析 NK 细胞及其 IFN-γ的表达水平,并检测 NK 细胞白细胞介素(IL)-12、IL-15、IL-18 受体的表达情况。

结果

急性 AOSD 患者 NK 细胞频率显著低于 HC,缓解 AOSD 患者 NK 细胞计数显著升高。急性 AOSD 患者 NK 细胞 IL-12、IL-15 受体表达显著增高,IL-18 受体表达无显著差异。急性 AOSD 患者 NK 细胞 IFN-γ表达显著高于 HC,缓解 AOSD 患者 IFN-γ表达显著降低。急性 AOSD 患者 NK 细胞和 IFN-γ表达 NK 细胞的绝对数与血清铁蛋白水平呈负相关。在 NK 细胞的 2 个不同亚群中,CD56 NK 细胞 IFN-γ表达显著高于 CD56 NK 细胞。

结论

在急性 AOSD 中,NK 细胞比例较低,但 IFN-γ产生能力较高,NK 细胞 IL-12、IL-15 受体表达上调可能促进 IFN-γ产生。此外,疾病活动度可能影响 AOSD 中 NK 细胞和 IFN-γ表达 NK 细胞的数量。

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