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免疫血栓的增加作为JAK抑制的关键机制,在类风湿性关节炎中与高凝血相关
Paula David1, Tom Macleod2, Ala Altaie2
1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Annals of the rheumatic diseases
|September 26, 2025
概括
雅努斯激酶抑制剂 (JAKi) 可能通过促进免疫血栓形成,增加风湿性关节炎 (RA) 中静脉血栓栓塞 (VTE) 风险. 这项研究表明,JAKi可以增强免疫细胞驱动的凝血,为RA患者的VTE提供了新的解释.
科学领域:
- 类风湿病学 类风湿病学
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 风湿性关节炎 (RA) 患者接受Janus激酶抑制剂 (JAKi) 治疗,风险增加的静脉血栓塞栓症 (VTE).
- 在RA中JAKi相关的VTE背后的机制尚未完全理解.
- 这项研究调查了JAKi是否在RA中促进免疫细胞驱动的凝血,称为免疫血栓症.
研究的目的:
- 研究JAK抑制剂在风湿性关节炎中增强免疫细胞驱动的凝血 (免疫血栓形成) 的潜力.
- 探索RA中JAKi相关免疫血栓的机制.
主要方法:
- 来自RA患者和健康对照组的外周血液白细胞 (PBL) 用JAK抑制剂治疗,并用Toll类受体激动剂刺激.
- 凝块形成和溶解动态使用血度试验进行了评估.
- 通过大量RNA测序,ELISA和基于珠子的免疫测试来探索机制.
主要成果:
- 托法西替尼治疗的PBL显著加速凝块形成,这取决于组织因子通路,并与增加的促血栓性细胞因子相关.
- 来自活跃的RA患者的PBL显示出更高的免疫血栓潜力.
- RNA测序揭示了JAKi诱导的NF-κB通路的激活,增加的组织因子和减少的抗凝因子.
- 抑制JAK1/氨酸激酶2,但不抑制JAK3,与血栓形成的增加有关.
- 许多患有JAK相关肺栓塞的RA患者表现出免疫血栓形成的迹象.
结论:
- 免疫血栓形成为类风湿性关节炎中与氏激酶抑制剂相关的静脉血栓栓塞症提供了一种新的机制解释.
- 针对特定的JAK途径可能会减轻接受JAKi治疗的RA患者的VTE风险.
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