免疫代谢受损的宿主血微环境 艾滋病毒感染导致失调的单细胞功能和突触传播ex vivo
Flora Mikaeloff1, Marco Gelpi2, Alejandra Escós1
1The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, 141 52, Sweden.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 27, 2025
概括
一项新的研究显示,44%接受治疗的艾滋病毒感染者 (PWH) 面临免疫代谢风险. 多omics数据确定了关键生物标志物和代谢干扰,导致PWH的慢性炎症和免疫细胞功能受损.
科学领域:
- 免疫代谢过程中的免疫代谢.
- 系统生物学 系统生物学
- 个性化医疗是个性化的医疗.
背景情况:
- 了解艾滋病毒治疗患者 (PWH) 的免疫代谢对于管理长期并发症至关重要.
- 在成功治疗的PWH中,很大一部分人仍然面临免疫代谢问题的风险.
研究的目的:
- 通过使用个性化,多omics方法来确定长期治疗PWH中免疫代谢并发症的机制.
- 根据免疫代谢风险对PWH进行分层.
主要方法:
- 血液细胞转录组学,血蛋白组学和COCOMO队列中的代谢组学的综合分析.
- 基于网络的患者分层和机器学习 (贝叶斯分类器) 用于生物标志物发现.
- 在初级细胞和皮质前脑器官 (FBO) 中进行功能测试,以验证代谢干扰.
主要成果:
- 44%的PWH被确定为免疫代谢并发症的风险组.
- 五种血蛋白生物标志物 (TBCB,GGCT,TXLNA,PLPBP,LATS1) 与风险有显著的相关性.
- 代谢模型预测了中央碳和托芬代谢中断的情况.
- 与持续的单细胞激活和功能障碍相关的代谢干扰.
- 在PWH血中的慢性炎症引起了FBO中的突触失调.
结论:
- 个性化的多组组学揭示了治疗PWH的独特免疫代谢风险概况.
- 已识别的生物标志物和代谢途径为干预提供了目标.
- 慢性炎症和代谢功能障碍有助于增加高危PWH患者心血管和神经精神疾病的风险.
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