Hepatitis C Virus and the Humoral Immune System

NCT ID: NCT00219999

Last Updated: 2013-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

161 participants

Study Classification

OBSERVATIONAL

Study Start Date

2001-09-30

Study Completion Date

2013-05-31

Brief Summary

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The purpose of this study is to measure specific chemokines, antibodies, and antibody-producing B cells in the blood of patients with hepatitis C virus (HCV) infection. Our hypothesis is that changes in chemokine levels affect the development of an effective immune response against HCV.

Detailed Description

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The long-term goal of our research is to understand why immune complexes (ICs) are produced in patients infected with HCV, and whether these complexes affect virus interaction with target cells. We have found that many patients infected with HCV have an increased frequency of circulating B cells, but no evidence that the increased B cells are activated of proliferating. One possible mechanism for such an increase would be a change in levels of chemokines that influence B cell localization and trafficking. Our studies are aimed at testing the following hypotheses:

1. One hypothesis is that HCV infection results in increased levels of specific cytokines and chemokines that may affect the motility and localization of immature and mature B cells. An alternative model is that HCV infection leads to chronic antigenic stimulation of B lymphocytes, and that the abnormalities of B cell function associated with HCV infection reflect this chronic antigenic stimulation.
2. A second hypothesis is that autoantibodies and immune complexes present in HCV patient serum contribute to the persistence and spread of viral infection.

To test these hypotheses, we are measuring levels of chemokines, the frequency of circulating B cells (mature resting B cells, mature activated B cells, memory B cells, and immature B cells), and the levels and components of ICs in the blood of HCV-infected patients. Controls include healthy volunteers and patients with chronic liver disease unrelated to HCV infection. No interventions in patient care are planned. When patients elect to undergo standard antiviral therapies under the supervision of their hepatologists, we will study the outcomes of therapy (no virologic response, partial or transient virologic response, sustained virologic response) to determine whether any of the observed alterations in chemokine levels, B cell frequency or activation, or immune complex levels correlate with the patient's response to antiviral therapy.

Conditions

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Hepatitis C Virus

Keywords

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Hepatitis Hepacivirus B Lymphocytes Chemokines Antibodies

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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HCV infection

current HCV infection, including intravenous drug users

No interventions assigned to this group

cryoglobulinemia

cryoglobulinemia and without HCV infection

No interventions assigned to this group

chronic liver disease

chronic liver disease not due to hepatitis C virus infection

No interventions assigned to this group

Sustained Virologic responders

successfully treated for HCV infection

No interventions assigned to this group

normal

normal, healthy volunteers

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Healthy volunteers, no liver disease
* Chronic infection with hepatitis C virus
* Other chronic liver disease unrelated to hepatitis C virus
* Subjects in all groups must have sufficiently healthy veins to allow blood collection.

Exclusion Criteria

* Any medical condition that, in the opinion of the investigators, precludes the patient's participation
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

New York Presbyterian Hospital

OTHER

Sponsor Role collaborator

Rockefeller University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lynn B Dustin, PHD

Role: PRINCIPAL_INVESTIGATOR

Rockefeller University

Locations

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Rockefeller University Hosital

New York, New York, United States

Site Status

Countries

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United States

References

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Charles ED, Green RM, Marukian S, Talal AH, Lake-Bakaar GV, Jacobson IM, Rice CM, Dustin LB. Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia. Blood. 2008 Feb 1;111(3):1344-56. doi: 10.1182/blood-2007-07-101717. Epub 2007 Oct 17.

Reference Type DERIVED
PMID: 17942751 (View on PubMed)

Related Links

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Other Identifiers

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R01AI060561

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LDU-0437

Identifier Type: -

Identifier Source: org_study_id