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.
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.


CONCLUSIONS
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.
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. mhashem@epi.umaryland.edu
Mohamed
M
Hashem
Hanaa
H
El-Karaksy
Mohamed T
MT
Shata
Maha
M
Sobhy
Heba
H
Helmy
Suzan
S
El-Naghi
Gehan
G
Galal
Zainab Z
ZZ
Ali
Gamal
G
Esmat
Sayed F
SF
Abdelwahab
G Thomas
GT
Strickland
Samer S
SS
El-Kamary
D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004534:Egypt; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000097:blood; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035781:Siblings
D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D007371:Interferon-gamma
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