2 December 2016
Although children can acquire chronic infection with hepatitis C virus (HCV), their risk is lower than adult patients. A study by Hugo Rosen and colleagues at the University of Colorado Denver in the US has now revealed features of the juvenile immune response that might contribute to more effective antiviral defence.
The vast majority of HCV infections occur in adults, with transmission occurring via shared needles or transfusion with contaminated blood. Children born to HCV-positive mothers can potentially contract the virus, and one recent study estimated that there are between 23,000 and 46,000 HCV-positive children in the US at present. However, children are also more likely than adults to eliminate the virus on their own, with 25-40% of paediatric patients achieving spontaneous viral clearance compared with around 20% of adult patients.
Little is known about the paediatric response to HCV infection, so Rosen’s team set out to profile the immune function of 16 HCV-positive children and adolescents relative to an equal number of healthy controls. Meanwhile, they examined 20 adults with HCV in order to distinguish age-related differences in the anti-HCV response.
All three groups of patients had similar numbers of T cells, the immune subpopulation that helps clear HCV infection. However, there were intriguing signs of differences in immune function between the various cohorts. Immune cells from HCV-positive children displayed clear evidence of an ongoing battle against the virus, whereas those from healthy children were more likely to be ‘naïve’ — meaning they had not yet been trained to respond to a specific infectious threat.
The differences relative to adults were more striking. One of the hallmarks of chronic infection is a phenomenon known as exhaustion, in which activated T cells gradually lose their ability to respond effectively to the virus. The researchers found that a key subset of T cells from HCV-positive children were more likely to produce proteins associated with ongoing immune activity, whereas those from adults tended to exhibit typical signatures of exhaustion.
These results offer evidence that the immune systems of younger patients may take longer to enter this exhausted state, giving them a better chance of successfully fighting off HCV infection. The authors caution that this is a relatively small study group, and that this more robust immune response could also be the result of a shorter infection duration relative to adults. Nevertheless, the results offer an intriguing potential explanation for the differences observed in the outcome of paediatric HCV infection.
Sheiko, M. A., Golden-Mason, L., Giugliano, S., Waasdorp Hurtado, C., Mack, C. L. et al. CD4+ and CD8+ T cell activation in children with hepatitis C. The Journal of Pediatrics. (2016).| article