Abstract：
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.
摘要：
I型干扰素（IFN-Is）在系统性红斑狼疮（SLE）发病机理中起重要作用。双重过滤血浆置换（DFPP）是SLE的一种治疗选择；然而，其对IFN-Is的影响尚不清楚。因此,我们研究了DFPP对IFN-Is的影响。使用基于细胞的报告系统分析了定期接受DFPP的SLE患者（n=11）的血浆，以检测IFN-I的生物利用度和诱导活性。测量血浆dsDNA的浓度，和蛋白质印迹分析用于评估STING途径的磷酸化。与健康对照相比，在患者中观察到更高的IFN-I生物利用度和诱导活性。DFPP后两个参数均下降。在具有高疾病活动性的患者中,IFN-I诱导活性的降低尤其显著。值得注意的是,在STING敲除的报告细胞中未观察到这种减少.此外,DFPP治疗后血浆dsDNA水平下降，这表明STING途径的抑制是观察到的活性降低的原因。Western印迹分析揭示DFPP后STING途径磷酸化的抑制。DFPP降低了IFN-I的生物利用度和血浆的诱导活性。这种减少可能归因于通过消除dsDNA对STING途径的抑制。
