NK Cell Deregulation in HBV Patients
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Using a multiparameter flow cytometry approach, we will assess the mean fluorescence intensity (MFI) of the listed molecules expressed on Natural Killer cells
研究概览
简要总结
Natural Killer (NK) cells play a large role in the innate immune response as they are equipped to kill infected or tumor cells. They express a panel of activating and inhibitory receptors that regulate the destruction of the target cell. Many reports have shown that NK cell function is suppressed in CHB patients. Exhaustion occurs when activating receptors become over stimulated leading to the loss of NK function. The investigators hypothesize that NK cells are rendered dysfunctional/ exhausted by HBV. The primary objective is to determined the phenotypical modifications and mechanisms associated to NK cell dysfunction, during different phases of CHB infection, in not treated patients.
详细描述
Using a previous cohort from the Limoges Hospital, the investigators have identified by multi-parametric flow cytometry phenotypic, cytokine and signaling molecules that are altered in NK cells from CHB patients during the inactive phase. Phenotypic changes observed include the downregulation of CD160, NKp30, CD16 and Tim-3. The expansion of 'adaptive' NK cells (FCεRg- NKG2C+ or CD57hi), and the upregulation of CD107a (steady state), NKG2D and 41BB. Functional changes include the decrease in the levels of IFNγ, TNFα and MIP1β. Cellular metabolism is now recognized to regulate functional properties of immune cells such as T or NK cells. The mammalian target of rapamycin (mTOR) kinase is a key regulator of cellular metabolism, integrating environmental cues to control downstream metabolic pathways. mTOR is the catalytic subunit of two different complexes: mTORC1 and mTORC2, the activity of which can be measured by measuring the level of phosphorylation of the proteins S6 and Akt respectively. The lab has previously shown that the mTOR pathway regulates NK cell development and activation 2. The investigators have observed that pS6 and pAkt are also decreased in CHB patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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
- •Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
- •Male or female, age ≥18 years
- •HBV infection or chronic HBV infection
- •Willing and able to provide written informed consent
- •Healthy donors must meet all of the following inclusion criteria to be eligible for participation in this study:
- •Male or female, age between 18 and 50 years
- •Willing and able to provide written informed consent
排除标准
- •Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
- •Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
- •Chronic liver disease of a non-HBV etiology
- •Immune or cancerous disease
研究组 & 干预措施
CHB patients
a blood sample is done during a follow-up visit
干预措施: blood sample CHB patients (Other)
Control group
a blood sample
干预措施: boold sample Control group (Other)
结局指标
主要结局
Using a multiparameter flow cytometry approach, we will assess the mean fluorescence intensity (MFI) of the listed molecules expressed on Natural Killer cells
时间窗: At inclusion, day 0
次要结局
未报告次要终点