NK Cell Deregulation in HBV Patients

NCT ID: NCT03761875

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-11
• Study Completion Date: 2024-03-31

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

CHB patients

a blood sample is done during a follow-up visit

Group Type: OTHER

blood sample CHB patients

Intervention Type: OTHER

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

Control group

a blood sample

Group Type: OTHER

boold sample Control group

Intervention Type: OTHER

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

Interventions

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

Intervention Type: OTHER

boold sample Control group

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Male or female, age ≥18 years
• HBV infection or chronic HBV infection
• Willing and able to provide written informed consent

• Male or female, age between 18 and 50 years
• Willing and able to provide written informed consent

Exclusion Criteria

• Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
• Chronic liver disease of a non-HBV etiology
• Immune or cancerous disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Limoges

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Véronique LOUSTAUD-RATTI, MD

Role: PRINCIPAL_INVESTIGATOR

Limoges Hospital

Uzma HASAN

Role: STUDY_DIRECTOR

Inserm U1111, Lyon

Locations

Limoges Hospital

Limoges, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Véronique LOUSTAUD-RATTI, MD

Role: CONTACT

veronique.loustaud-ratti@unilim.fr

+33 5 55 05 66 84

Sophie ALAIN, MD

Role: CONTACT

sophie.alain@unilim.fr

05 55 05 67 28

Facility Contacts

Véronique LOUSTAUD-RATTI, MD

Role: primary

veronique.loustaud-ratti@unilim.fr

+33 5 55 05 66 84

Other Identifiers

87RI18-0021

Identifier Type: -

Identifier Source: org_study_id