Strong Hepatitis C Virus (HCV)–specific Cell-mediated Immune Responses in the Absence of Viremia or Antibodies Among Uninfected Siblings of HCV Chronically Infected Children

[Guest guest]

http://jid.oxfordjournals.org/content/203/6/854.abstract?etoc

Journal of Infectious Diseases

Volume203, Issue6 Pp. 854-861

Strong Hepatitis C Virus (HCV)–specific Cell-mediated Immune Responses in the

Absence of Viremia or Antibodies Among Uninfected Siblings of HCV Chronically

Infected Children

Mohamed Hashem1,2, Hanaa El-Karaksy3, Mohamed T. Shata4, Maha Sobhy2, Heba

Helmy3, Suzan El-Naghi5, Gehan Galal2, Zainab Z. Ali2, Gamal Esmat6, Sayed F.

Abdelwahab2,7, G. Strickland1,a and Samer S. El-Kamary1,a

1Department of Epidemiology and Public Health, University of land School of

Medicine, Baltimore, land

4Division of Digestive Diseases, Department of Internal Medicine, University of

Cincinnati School of Medicine, Cincinnati, Ohio

2Egyptian Company for Blood Transfusion Services, Holding Company for Biological

Products and Vaccines, Giza

3Department of Pediatrics

6Department of Tropical Medicine and Hepatology, Faculty of Medicine, Cairo

University

5Department of Pediatrics, National Hepatology and Tropical Medicine Research

Institute, Cairo

7Department of Microbiology and Immunology, Faculty of Medicine, Minia

University, Minia, Egypt

Reprints or correspondence: Mohamed Hashem, M.B., B.Ch, Assistant Professor,

Department of Epidemiology and Public Health, University of land School of

Medicine, 660 W Redwood St, HH101, Baltimore, MD 21201

(mhashem{at}epi.umaryland.edu).

Abstract

Background. Cell-mediated immune (CMI) responses to hepatitis C virus (HCV)

antigens in adults without seroconversion or viremia are biomarkers for prior

transient infection. We investigated HCV-specific CMI responses in seronegative

children living with HCV-infected siblings.

Methods. Children 3–18 years of age living with HCV-infected siblings were

screened for HCV antibodies and HCV RNA. Peripheral blood mononuclear cells

(PBMCs) were evaluated for HCV-specific CMI responses by interferon γ (IFN-γ)

enzyme-linked immunospot assay using 3 recombinant HCV protein antigens. Flow

cytometry phenotypically characterized IFN-γ-secreting cells.

Results. Forty-five seronegative children and 5 seropositive viremic siblings

had functionally viable PBMCs. Among the 45 seronegative siblings, 15 (33.3%)

had positive HCV-specific IFN-γ responses, and subsequent RNA testing revealed

that 3 were viremic. Compared with the 5 seropositive viremic children, the

median number of HCV-specific spot-forming units was significantly higher in the

12 seronegative aviremic children (P = .002) and in the 3 seronegative viremic

children (P = .025). Flow cytometric analysis revealed that IFN-γ was

synthesized mainly by CD4+ T cells.

Conclusion. Strong HCV-specific CD4+ T cell responses were detectable in

higher frequency among seronegative, aviremic children compared with

persistently infected siblings. Further studies are needed to determine whether

these immune responses are protective against HCV infection.

Received May 24, 2010.

Accepted October 29, 2010.

© The Author 2011. Published by Oxford University Press on behalf of the

Infectious Diseases Society of America. All rights reserved. For

Permissions, please e-mail: journals.permissions@...