Hepatitis C virus-specific cell-mediated immune responses in children born to mothers infected with hepatitis C virus

Abstract

Objective: To investigate the association between hepatitis C virus (HCV)-specific cell-mediated immunity (CMI) responses and viral clearance in children born to mothers infected with HCV.

Study design: A cross-sectional study of children from a mother-infant cohort in Egypt were enrolled to detect CMI responses to recombinant core and nonstructural HCV antigens (nonstructural segments NS3, NS4a/b, and NS5 of the HCV genome) using an interferon-gamma enzyme-linked immunospot assay. Children born to mothers with chronic HCV were enrolled into 3 groups: transiently viremic (n = 5), aviremic (n = 36), and positive control (n = 6), which consisted of 1 child with chronic HCV from this cohort and another 5 children with chronic HCV from a companion study. Children without HCV born to mothers without HCV (n = 27) served as a negative control group. Wilcoxon rank sum test was used to compare the magnitude of CMI responses between groups.

Results: None of the 6 control children who were positive for HCV responded to any HCV antigen, and 4 (80%) of 5 children with transient viremia responded to at least one HCV antigen, compared with 5 (14%) of 36 and 3 (11%) of 27 children in the aviremic and negative control groups, respectively. Children with transient viremia elicited stronger responses than did negative controls (P = .005), positive controls (P = .011), or children without HCV viremia (P = .012), particularly to nonstructural antigens.

Conclusions: HCV-specific CMI responses were significantly higher in magnitude and frequency among transiently infected children compared with those persistently infected. This suggests CMI responses may be associated with past viral clearance and can identify children at high risk of infection, who can be targeted for health education, screening, and follow-up.

Figure

Median number of SFCs per 1 million PBMCs were quantified using an IFN-γ mini-ELISPOT assay and displayed by subgroup in response to stimulation with the 3 HCV-specific antigens. The lower and upper borders of each box encompass the IQR, the horizontal line inside the box represents the median, the vertical lines from the ends of each box extend to the extreme data points, and the asterisks represent outliers. The subgroups are: (1) positive control children with seropositive-persistent viremia (n = 6); (2) seronegative aviremic children born to mothers infected with HCV (n = 36); (3) children with seronegative transient viremia born to mothers infected with HCV (n = 5); and (4) a negative control group (children and their mothers not infected with HCV) (n = 27). In panels P values compare the magnitude of CMI responses of the transiently viremic group to the other subgroups for the A, core B, NS3/NS4 and C, NS5 antigens.