NCT03761875

NK Cell Deregulation in HBV Patients

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: University Hospital, Limoges · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Hepatitis B Virus

Interventions

Type	Name	Description
OTHER	blood sample CHB patients	During a boold sample at only one follow up visit: * 3 tubes EDTA 10 ml per patient * 1 tube "Paxgene" 1ml * 1 dry tube per patient
OTHER	boold sample Control group	* 2 tubes EDTA ideally age and sex matched to CHB patient. * 1 tube "Paxgene" 1ml * 1 dry tube

Timeline

• Start date: 2018-12-11
• Primary completion: 2023-12-01
• Completion: 2024-03-01
• First posted: 2018-12-03
• Last updated: 2023-05-06

Locations

1 site across 1 country: France