Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus.

OBJECTIVES: Vertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates. DESIGN: To address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age. RESULTS: As expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines. CONCLUSION: Our data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.

Lack of Association Between Interleukin 28B Polymorphism and Vertical Transmission of Hepatitis C.

OBJECTIVES: Single genetic nucleotide polymorphism (rs12979860) near the gene for interleukin 28B (IL28B) is known to be of importance for frequency of spontaneous clearance and treatment outcome in interferon-based therapies in patients with hepatitis C virus (HCV) infection. The aim of the present study was to investigate whether IL28B polymorphism in children and/or their mothers plays a role in vertical transmission of HCV (HCV-VT). METHODS: Plasma samples from 59 infected women, 76 uninfected children born to infected mothers, and 47 children with known vertically transmitted HCV infection, were analysed for IL28B polymorphism and classified by the IL28B genotype (C/C, C/T, and T/T) and by viral genotype. RESULTS: The proportion of children with genotype C/C was the same in the vertically infected (36%, 17/47) and the exposed uninfected children (38%, 29/76). No difference was seen when stratifying for viral genotype. There was no association between mothers' IL28B genotype and the risk of vertical transmission. CONCLUSIONS: Regardless of viral genotype we found no association between IL28B genotype and the risk of HCV-VT. The IL28B genotype CC, which has been shown to be favourable in other settings, was not protective of HCV-VT. Thus, other factors possibly associated with the risk of HCV-VT need to be explored.