Changes in Adaptive B Cell Response in Infants Exposed, Uninfected With HCV

Exposure to, and infection with hepatitis C virus (HCV) in infants may cause disparate effects on adaptive B cells and innate immune cells, such as myeloid cells and natural killer cells, according to results of a study published in Gut.

A major source of chronic hepatitis C in children is mother-to-child transmission of HCV; previous literature has shown that up to 20% of exposed infants (ie, those born to women positive for HCV RNA), demonstrate HCV RNA within 3 months postpartum. However, chronic infection with HCV among children of mothers with HCV is rare, indicating the existence of mechanisms for viral clearance. In fact, HCV-specific T cell responses have been observed in uninfected infants born to mothers with HCV viremia, suggesting that the immune system of the exposed infants are contributing to transmission rates. However, it is unknown if B cell-mediated immune responses develop after vertical HCV exposure.

Therefore, researchers studied B cells, innate immune cells, and soluble factors in 55 infants who were either unexposed, exposed uninfected, or infected with HCV; infants were followed through 18 months postpartum. All mothers were positive for HCV antibodies; 40 of the 55 mothers were positive for HCV RNA at the time of delivery.

Results showed that anti-HCV immunoglobulin (Ig) G secreting B cells are present in children after vertical transmission of HCV infection. In addition, results showed that low, but clearly detectable levels of anti-HCV IgG secreting B cells were observed in children exposed to, but uninfected with HCV. Moreover, prenatal and perinatal HCV-exposure were linked to the induction of early maturation of the B cell compartment, as well as B cell activation. Specifically, results showed that found that a significantly increased percentage of IgA-positive plasma cells among children exposed but uninfected with HCV compared with unexposed children (29.7% vs 15.1%, P = .01). However, no further increase in the percentage of IgA-positive plasma cells was observed in children with (28.9%), despite their slightly older age. A similar trend was observed for IgG positive plasma cell (1.87%, 3.15% and 1.95% for unexposed, exposed uninfected and infected children, respectively). In contrast, alterations within myeloid immune cells, natural killer cells, or inflammatory serum cytokines were only visible in children with HCV.

The study authors concluded, “These findings of HCV-specific memory B cells and an altered B cell subset composition in some HCV-exposed but uninfected children illustrate that in utero HCV-exposure impacts the development of an adaptive B cell response.” They added, “This response might be of importance for protection against vertical transmission of HCV and stresses the importance of identifying and treating women of childbearing age before they become pregnant.”

Reference

Lutckii A, Strunz B, Zhirkov A, et al. Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus [published online April 27, 2020]. Gut. doi:10.1136/gutjnl-2019-320269