双滤过血浆置换可降低系统性红斑狼疮患者的 I 型干扰素生物利用度和诱导活性。

IF 2.7 Q3 IMMUNOLOGY
Immunological Medicine Pub Date : 2024-12-01 Epub Date: 2024-07-01 DOI:10.1080/25785826.2024.2372918
Takumi Saito, Ryo Takatsuji, Goh Murayama, Yu Yamaji, Yukitomo Hagiwara, Yujin Nishioka, Taiga Kuga, Tomoko Miyashita, Makio Kusaoi, Naoto Tamura, Ken Yamaji
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引用次数: 0

摘要

I 型干扰素(IFN-Is)在系统性红斑狼疮(SLE)发病机制中发挥着重要作用。双滤过血浆置换术(DFPP)是治疗系统性红斑狼疮的一种方法,但它对IFN-Is的影响仍不清楚。因此,我们研究了 DFPP 对 IFN-Is 的影响。我们使用基于细胞的报告系统分析了定期接受DFPP治疗的系统性红斑狼疮患者(n = 11)的血浆,以检测IFN-Is的生物利用度和诱导活性。血浆中dsDNA的浓度也得到了测定,并通过Western印迹分析评估了STING通路的磷酸化情况。与健康对照组相比,患者的 IFN-I 生物利用率和诱导活性更高,而这两个参数在 DFPP 治疗后都有所下降。IFN-I诱导活性的降低在疾病活动度高的患者中尤为明显。值得注意的是,在 STING 基因敲除的报告细胞中没有观察到这种降低。此外,血浆dsDNA水平在DFPP治疗后也有所下降,这表明STING通路的抑制是导致所观察到的活性下降的原因。Western印迹分析显示,DFPP抑制了STING通路的磷酸化。DFPP 降低了 IFN-I 的生物利用度和血浆的诱导活性。这种降低可能是由于dsDNA的消除抑制了STING通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Double-filtration plasmapheresis reduces type I interferon bioavailability and inducing activity in systemic lupus erythematosus.

Type I interferons (IFN-Is) play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Double-filtration plasmapheresis (DFPP) is a treatment option for SLE; however, its effect on IFN-Is remains unclear. Therefore, we investigated the effects of DFPP on IFN-Is. Plasma from patients with SLE (n = 11) who regularly underwent DFPP was analysed using a cell-based reporter system to detect the bioavailability and inducing activity of IFN-I. The concentration of plasma dsDNA was measured, and western blotting analysis was used to assess the phosphorylation of the STING pathway. A higher IFN-I bioavailability and inducing activity were observed in patients compared to healthy controls, and both parameters decreased after DFPP. The reduction in IFN-I-inducing activity was particularly prominent in patients with high disease activity. Notably, this reduction was not observed in STING-knockout reporter cells. Additionally, plasma dsDNA levels decreased after DFPP treatment, suggesting that inhibition of the STING pathway was responsible for the observed decrease in activity. Western blotting analysis revealed suppression of STING pathway phosphorylation after DFPP. DFPP reduced IFN-I bioavailability and the inducing activity of plasma. This reduction is likely attributable to the inhibition of the STING pathway through the elimination of dsDNA.

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来源期刊
Immunological Medicine
Immunological Medicine Medicine-Immunology and Allergy
CiteScore
7.10
自引率
2.30%
发文量
19
审稿时长
19 weeks
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