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T Regulatory Cells in Hepatitis c Infected Patients

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ClinicalTrials.gov Identifier: NCT03186235
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Esraa Hassan,MD, Assiut University

Brief Summary:
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 .

Condition or disease Intervention/treatment
Hepatitis C Other: Flow cytometry

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.


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Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Other
Time Perspective: Cross-Sectional
Official Title: Regulatory T Cells and Their Cytokines Profile in Different Groups of Hepatitis c Infected Patients: Across Sectional Study
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : August 1, 2019
Estimated Study Completion Date : September 15, 2019

Resource links provided by the National Library of Medicine


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 : 18 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




Primary Outcome Measures :
  1. 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



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes 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
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186235


Contacts
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Contact: Prof. Noha Abdelhalim Afifi, Proffesor 01006261108 noafifi2000@yahoo.com
Contact: esraa hassan mohamed, demonestrator 01006306349 dresraahassan91@gmail.com

Locations
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Egypt
Assiut University Recruiting
Assiut, Egypt
Sponsors and Collaborators
Assiut University

Publications:

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Responsible Party: Esraa Hassan,MD, Principle Investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03186235     History of Changes
Other Study ID Numbers: oosa
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections