NK Cell Deregulation in HBV Patients (LiNKeB)

May 4, 2023 updated by: University Hospital, Limoges
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: CHB patients
a blood sample is done during a follow-up visit
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: Control group
a blood sample
Other: boold sample Control group
  • 2 tubes EDTA ideally age and sex matched to CHB patient.
  • 1 tube "Paxgene" 1ml
  • 1 dry tube

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Using a multiparameter flow cytometry approach, we will assess the mean fluorescence intensity (MFI) of the listed molecules expressed on Natural Killer cells
Time Frame: At inclusion, day 0
At inclusion, day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Limoges

Investigators

  • Principal Investigator: Véronique LOUSTAUD-RATTI, MD, Limoges Hospital
  • Study Director: Uzma HASAN, Inserm U1111, Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2018

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

November 12, 2018

First Submitted That Met QC Criteria

November 29, 2018

First Posted (Actual)

December 3, 2018

Study Record Updates

Last Update Posted (Estimate)

May 5, 2023

Last Update Submitted That Met QC Criteria

May 4, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 87RI18-0021

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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