在接受Janus激酶抑制剂治疗的RA患者中NK细胞和耗尽的Th细胞表型的变化:对副作用的含义
Juan José Fernández-Cabero1, Carmen Lasa-Teja1,2, David San Segundo1,3
1Immunopathology Group, Instituto de Investigación Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain.
International journal of molecular sciences
|June 13, 2025
概括
简氏激酶抑制剂 (JAKis) 改变了类风湿性关节炎 (RA) 患者的免疫细胞,减少NK Dim细胞和转移T细胞群. 这可能会增加JAKis治疗RA患者感染和恶性瘤的风险.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 风湿性关节炎 (RA) 是一种慢性自身免疫性疾病.
- 简氏激酶抑制剂 (JAKis) 是一种用于治疗RA的药物.
- 对JAKis的安全性概况存在担忧,特别是潜在的不良事件,如感染和恶性瘤.
研究的目的:
- 研究JAKis对RA患者免疫细胞子集的影响.
- 为了识别由JAKis诱导的特定免疫细胞改变.
- 为了将这些变化与RA患者的潜在不良事件相关联.
主要方法:
- 该研究包括78名接受JAKis治疗的RA患者,20名健康捐赠者和20名接受bDMARD治疗的RA患者.
- 使用多参数流细胞计分析了周围血液单核细胞 (PBMC).
- 进行了先天性和适应性免疫细胞子集的表征.
主要成果:
- 接受JAKi治疗的RA患者显示细胞毒性NK Dim细胞减少,NK Dim细胞上激活标记物Nkp30的表达减少.
- 在JAKi组中观察到Th17,Th1-17和中央记忆 (CM) CD4+T细胞的显著减少.
- 与对照组相比,在接受JAKi治疗的患者中发现了效应记忆 (EM) 和终端分化的CD45RA (TEMRA) CD4+ T细胞的增加.
结论:
- 在RA患者中,JAKis诱导免疫细胞群的显著变化.
- 观察到NK Dim和Th1-17细胞的减少,以及耗尽Th子集的增加,可能会损害抗病毒免疫力.
- 与JAKi治疗相关的这些免疫变化可能会导致RA患者感染和恶性病的风险增加.
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