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在接受ART治疗的HIV患者中,NF-κB依赖基因表达和血IL-1β,TNFα和GCSF驱动了转录组多样性和CD4:CD8比率

Yingfan Wang¹, German G Gornalusse^2,3, David A Siegel⁴

¹Department of Computer Science, Duke University, Durham, North Carolina, United States of America.

bioRxiv : the preprint server for biology

|February 24, 2025

概括

接受抗逆转录病毒疗法 (ART) 的艾滋病毒感染者表现出与炎症和免疫恢复相关的独特免疫特征,而不是艾滋病毒储存量大小. 识别这些子组可能会改善与艾滋病相关的免疫功能障碍的治疗策略.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
基因组学就是基因组学.

背景情况:

尽管有抗逆转录病毒疗法 (ART),但与艾滋病毒阴性个体相比,艾滋病毒感染者 (PWH) 患病率和死亡率增加,可能是由于持续的艾滋病毒导致的慢性炎症.
了解在ART上PWH中的宿主免疫特征对于改善免疫恢复和临床结果至关重要.

研究的目的:

在ART上的PWH的外围CD4+T细胞中识别不同的宿主免疫特征.
为了将这些特征与免疫恢复标记 (CD4:CD8比率) 和艾滋病毒持久性相关联.
探索特定的血免疫标记物在塑造CD4+T细胞转录组多样性的作用.

主要方法:

在ART上从154个PWH中对外围CD4+T细胞进行大量RNA测序 (RNA-seq).
血免疫标记水平的量化.
用对控制的多重近似方法 (PaCMAP) 进行尺寸缩小和集群的应用.
对与细胞相关的HIVDNA和RNA进行分析,以确定HIV储存体的大小.

主要成果:

在ART的PWH中发现了三个不同的转录组群,主要由由NF-κB调节的差异性基因表达定义.
这些群体与CD4:CD8比率 (免疫恢复标志物) 相关,但与HIV储存量大小无关.
特定的血免疫标记物,包括IL-1β,TNF-α和GCSF,在集群中显示出不同的模式,与CD4+T细胞转录组多样性和免疫恢复相关.

结论:

在ART上确定了具有独特免疫特征的PWH的新子组.
在ART上定义了PWH中与临床显著的免疫参数相关的转录特征.
这些发现可能会为开发先进的临床策略提供信息,以解决与艾滋病相关的免疫功能障碍.

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