NK Cell Deregulation in HBV Patients

Hepatitis B Virus Clinical Trial

— LiNKeB  

Official title:

NK Cell Deregulation in HBV Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03761875
• Other study ID #: 87RI18-0021
• Status: Recruiting
• Phase: N/A
• Start date: December 11, 2018
• Est. completion date: March 2024

Study information

• Verified date: May 2023
• Source: University Hospital, Limoges
• Contact: Véronique LOUSTAUD-RATTI, MD
• Phone: +33 5 55 05 66 84
• Email: veronique.loustaud-ratti[@]unilim.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B
• Hepatitis B Virus

Intervention

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
• boold sample Control group
2 tubes EDTA ideally age and sex matched to CHB patient. 1 tube "Paxgene" 1ml 1 dry tube

Locations

Country	Name	City	State
France	Limoges Hospital	Limoges

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Using a multiparameter flow cytometry approach, we will assess the mean fluorescence intensity (MFI) of the listed molecules expressed on Natural Killer cells		At inclusion, day 0