Abstract
Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control.
Highlights
Perinatal transmission of hepatitis B virus (HBV) is the most common mode of transmission world-wide
We found no significant difference in the proportions of total circulating natural killer (NK) cells (CD56+CD3−) or CD56bright CD16−/dim, CD56dim CD16+ and CD56–CD16+ NK cell subsets between the two groups (Fig. 1a,b)
To evaluate whether there were any perturbations in the proportions of NK cell subsets according to disease activity, results were analysed according to HBeAg status, viral load and levels of alanine transaminase (ALT)
Summary
Perinatal transmission of hepatitis B virus (HBV) is the most common mode of transmission world-wide. Despite the availability of an effective prophylactic vaccine, HBV infection during infancy or early childhood is common in areas of high endemicity. In these regions, mother-to-infant transmission accounts for approximately 50% of chronic infections. Our knowledge of the natural history of paediatric HBV infection is severely limited by the difficulty in sampling this group and agematched controls. This has led to the widely held view that immunotolerant children are unlikely to respond to antiviral therapy. In this study we have focused on natural killer (NK) cells, a critical component of anti-viral defence, enriched in the liver and shown to be dysregulated in adult CHB
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