HCV-Exposed, Uninfected Infants Show B-Cell Changes

By Anne Harding

April 29, 2020

NEW YORK (Reuters Health) - Many uninfected babies born to mothers with chronic hepatitis C virus (HCV) infection may have already fought off the virus themselves, new research suggests.

Infants exposed to the virus but not infected had immune system changes similar to those of HCV-infected infants, including high numbers of virus-specific IgG-secreting B cells, more IgA-positive plasma cells and upregulation of CD40, compared with unexposed and uninfected infants, Dr. Niklas K. Bjoerkstroem of Karolinska University Hospital in Stockholm and colleagues found.

"It seems to be a specific thing that happens within the B cells within these exposed children," Dr. Bjoerkstroem told Reuters Health by phone. "It gives us some insight into why it's such a rare instance that hepatitis C is vertically transmitted."

The risk of mother-to-child transmission (MTCT) in pregnant women with HCV is not clear, but it is estimated at approximately 5%, lower than for chronic hepatitis B virus and HIV, Dr. Bjoerkstroem and his team note in Gut.

Some uninfected children born to mothers with HCV have HCV-specific T-cell responses, they add. To investigate B-cell-mediated immunity and HCV exposure, the authors looked at 55 mothers and their babies delivered at a hospital in Saint Petersburg, Russia, from 2012 to 2016. Infants underwent peripheral blood mononuclear cell (PBMC) sampling at birth and at six, 12 and 18 months.

Forty of the mothers were HCV-RNA positive when the babies were born and 15 were negative, indicating that they had cleared the virus. Their infants were classified as unexposed. Among the 40 exposed infants, three became HCV-RNA positive during the follow-up period, and were classified as infected.

Children who became infected had higher mean levels of HCV-specific Ig-G secreting B cells than the children who were exposed but uninfected and the unexposed group. Mean levels of HCV-specific Ig-G secreting B cells were similar for the exposed but uninfected and the unexposed groups, but some exposed individuals had "robust responses."

IgA-positive plasma cells were identified in 28.9% of infected children, 29.7% of exposed children and 15.1% of unexposed children, with a similar pattern for IgG-positive plasma cells.

Infected children also had changes in myeloid immune cells and natural killer cells and a soluble factor profile with high levels of inflammatory cytokines and chemokines, none of which were seen in the exposed group.

These inflammatory changes, indicating a "constant low level of activation," may have already occurred in the infants who were exposed but not infected, Dr. Bjoerkstroem noted.

While excellent, safe drugs are now available to eliminate HCV within weeks, he said, people can be reinfected if they are exposed again, for example intravenous drug users and prisoners. "All those people are still completely vulnerable to the possibility of becoming reinfected."

Since the study was conducted, new tools have become available including single-cell sequencing, which allows investigators to sequence all of the RNA molecules within a cell, he said. "Downstream projects here are again to find these specific B cells in the exposed children and pull those and really interrogate them using complex novel methods."

SOURCE: https://bit.ly/2yLZIYE Gut, online April 27, 2020.