T Regulatory Cells in Hepatitis c Infected Patients

December 16, 2019 updated by: Esraa Hassan,MD, Assiut University

Regulatory T Cells and Their Cytokines Profile in Different Groups of Hepatitis c Infected Patients: A Case Control Study

Chronic hepatitis C infection is a global worldwide health problem with an increasing burden year-by-year, particularly in areas with a high endemicity like Egypt . The World Health Organization estimates that approximately 200 million people worldwide are infected with hepatitis c virus. In Egypt, it was estimated that 15 % of Egyptians have serologic evidence of hepatitis C viral infection .

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The ultimate outcome of hepatitis c viral infection is determined by the host immune response. Patients with acute hepatitis c viral infection who did not clear the virus developed chronicity. Persistant hepatitis c virus -specific cytotoxic T-cell responses in the liver have been associated with the development of hepatic inflammation which may ultimately lead to liver cirrhosis. One of the potential mechanisms that might modulate hepatitis c virus -specific immune responses is the inhibitory role of the regulatory T cells.

Regulatory T cells are a subtype of T-cells that play a fundamental role in maintaining immune homeostasis to balance between the tissue-damaging and protective effects of the immune response. Regulatory T cells are characterized by the expression of the Forkhead box protein P3 transcription factor in the nucleus and is generally accepted as the single best marker for regulatory Tcells. In cases of hepatitis c virus infection, the role of regulatory Tcells is still controversial and most of studies yielded conflicting reports. This conflict may be explained by the heterogeneity in the methods and sites of studying the frequency of regulatory T cells.

There are strong evidences that regulatory T cells and their cytokines may play an important role in the induction of tolerance in the liver.

Interleukin 35 is an immune-suppressive cytokine expressed in stimulated human regulatory Tcells during inflammatory responses and consists of Interlukin-12a ( Interleukin 12p35 subunit) and IL-27b chains, encoded by the Interleukin 12A and Epstien Bar I3 genes, respectively. It is a novel heterodimeric cytokine belonging to the Interleukin 12 family, and little is known about its receptor. Activated peripheral blood mononuclear cell (PBMC)- derived human regulatory T cells have been shown to express and secrete large amounts of Interleukin 35, which contributes significantly to the suppressive capacity of regulatory T cells in an Interlukin 35-dependent manner.

Additionally, human regulatory T cell -derived IL35 is required for the conversion of human conventional cluster of differentiation 4+Foxp3_ T cells into induced T regulatory 35 cells, which then promote the generation of more induced T regulatory 35 cells via Interleukin 35 secretion, resulting in infectious tolerance (18). In addition, Interleukin 35 has been shown to suppress the T helper (Th) cells Th1 and Th17.

In this study, investigators will evaluate the possible role of regulatory T cells and their cytokines in different groups of hepatitis c infected patients by investigating the frequency of regulatory T cells and serum level of IL35 and examining their relationship to the various patterns of hepatitis c viral persistence, hepatitis c virus pathogenesis, complications with cirrhosis and hepatocellular carcinoma in an attempt to estimate the future value of using anti IL35 and regulatory T cell depletion in those patients.

Study Type

Observational

Enrollment (Actual)

88

Contacts and Locations

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

Study Locations

  • Egypt
      • Assiut, Egypt
        • Assiut University

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

. All participants were recruited from Assiut Liver Institute for Treatment of Hepatitis C Virus and Assiut University Hospitals outpatient clinics, Assiut, Egypt. Healthy donors will be attending blood bank of Assiut University Hospital during the study period. They will be negative for known serologic markers of hepatitis (B & C) including hepatitis B surface antigen and antibodies to Hepatitis C virus

Description

Inclusion Criteria:

  • positive for hepatitis c viral antibodies by Enzyme Linked Immuno Sorbent Assay and by hepatitis c viral Ribo Nucleic Acid Real time Polymerase Chain Reaction

Exclusion Criteria:

  • are pregnancy, history of Schistosoma infection, inflammatory bowel diseases or suspected inflammatory bowel diseases , autoimmune diseases including rheumatoid arthritis, and any patients on systemic immunomodulators

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group I : 18 healthy controls
Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA.
Other: Flow cytometry
Isolation of T regulatory cells from blood
group II : 16 Hepatitis C infected patients (naïve)
Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA.
Other: Flow cytometry
Isolation of T regulatory cells from blood
group III:18 HCV-infected patients complicated with cirrhosis
Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA.
Other: Flow cytometry
Isolation of T regulatory cells from blood
group IV: 18 HCV-infected patients with Hepatocellular cancer
Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA.
Other: Flow cytometry
Isolation of T regulatory cells from blood
Group V:18 patients with sustained viral response (SVR).
Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA.
Other: Flow cytometry
Isolation of T regulatory cells from blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
frequency of T regulatory cells in all 6 groups using flow cytometry
Time Frame: An average 1 year
frequency of T regulatory cells will be estimated by flow cytometry in all 6 groups
An average 1 year

Collaborators and Investigators

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

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

July 1, 2018

Primary Completion (Actual)

August 1, 2019

Study Completion (Actual)

August 1, 2019

Study Registration Dates

First Submitted

June 10, 2017

First Submitted That Met QC Criteria

June 13, 2017

First Posted (Actual)

June 14, 2017

Study Record Updates

Last Update Posted (Actual)

December 18, 2019

Last Update Submitted That Met QC Criteria

December 16, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Esraa

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Clinical Trials on Hepatitis C

Clinical Trials on Flow cytometry

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe