2000HIV Trained Innate Immunity in HIV Elite Controllers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 3
- 主要终点
- Direct cytokine responses
研究概览
简要总结
Some individuals are able to spontaneously control HIV replication, the so-called 'elite controllers' (ECs). ECs are crucial for our understanding of HIV infection. While there is more and more evidence pointing towards a role of the innate immune system in elite control, no research has been performed on the role of innate trained immunity in elite control of HIV.
In this cross-sectional case-control study, we will study this role of trained immunity in HIV elite control by comparing ECs both to a non-HIV-infected first-degree relative, and to HIV patients who are not elite controllers. In addition, we will study whether HIV itself can induce a trained innate immunity phenotype.
详细描述
Rationale:
It remains unknown how some individuals spontaneously control HIV in the absence of antiretroviral medication, called HIV 'elite controllers' (ECs). ECs have been absolutely crucial to our current understanding of control of HIV replication. While research has mainly focused on the adaptive immune system, there is a vast amount of evidence indicating that the innate immune system is essential to HIV elite control.
Trained innate immunity can be expressed in terms of enhanced responsiveness of innate immune cells to a repeated trigger. This occurs through epigenetic remodeling after exposure to certain stimuli, such as beta-glucan, lipopolysaccharide (LPS) or the bacillus Calmette-Guérin (BCG) vaccine. Innate training results in an altered gene expression and metabolic reqiring on a cellular level, resulting in greater resistance against subsequent infection.
Both the impact of trained immunity on HIV infections and vice versa, the impact of HIV on trained immunity, are unknown. Our hypothesis is that ECs are natural hyper-responders to innate immune training triggers and that this aids in the HIV elite control phenotype.
Objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Direct cytokine responses
时间窗: 24 hour ex vivo experiment
Isolated monocytes and NK-cells will be stimulated ex vivo with a range of stimuli. Cytokines released in the supernatants will be measured by ELISA.
Cytokine responses after 6-day training
时间窗: 7 day ex vivo experiment
Isolated monocytes and NK-cells will be trained ex vivo and the innate training effect will be studied after restimulation with an unrelated stimulus on day 7. Cytokines released in the supernatant and intracellularly will be measured by ELISA.
Transcriptome
时间窗: 1 year after sample collection
RNA in the cells will be analysed to gain a transcriptional signature.
Epigenome
时间窗: 1 year after sample collection
Epigenetic signatures will be studied by means of ChIP sequencing and ATAC sequencing.
Immune phenotyping
时间窗: 1 year after sample collection
Circulating cells are phenotyped by menas of elaborate flow cytometry panels.
次要结局
未报告次要终点