ERV-3 envelope expression and congenital heart block: What does a physiological knockout teach us

Congenital heart block is a serious condition with significant mortality due in most cases to the transplacental transfer of autoantibodies from an otherwise asymptomatic mother. Although SSA/Ro and SSB/La autoantibodies have been implicated, attention has focused recently on autoantibodies to envelope proteins of endogenous retrovirus-3 (ERV-3). We have recently described a natural knock out model for ERV-3 involving severely truncated form of the protein due to a premature stop mutation. If a pregnant female homozygous for the truncated form of the ERV-3 carries a foetus expressing the entire protein, the mother might be expected to acquire high titre immunity, while the foetus homozygous for the truncated form would not be expected to immunise its mother. In order to test whether this naturally occurring model could shed light on the ETO pathogenesis of CHB, we tested the ERV-3 stop polymorphism's in the mothers of 12 CHB infants, but not was homozygous for the stop mutation. These data tend to rule out a role for the stop polymorphism in the generation of antibodies to ERV-3 during pregnancy, but not that other polymorphism's might be responsible.