Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream

Background: Cytomegalovirus (CMV) is the major cause of congenital infection and disease leading to permanent birth defects. In about 35-40% of pregnant women with primary CMV infection, virus crosses the placenta, resulting in the birth of congenitally infected babies. In contrast, this happens in only 1-3% of seropositive women with strong CMV-specific humoral immunity. Whether CMV reaches the fetus and disseminates depends on the level of high-avidity antibodies in the maternal circulation and the passive immunity of the fetus. Objectives and study design: To identify CMV infection in uncomplicated deliveries based on detection of viral DNA in placental biopsy specimens at term. To quantify CMV-specific IgG avidity, neutralizing titer, IgG1 concentration, and characterize the immunoblot profiles for CMV proteins in paired samples of placental and cord blood sera. Results: In accord with earlier reports, CMV DNA was detected in 39% (11/28) of placentas with mean-to high-avidity CMV-specific IgG. In seropositive women, the concentration of antiviral antibodies, specifically IgG1, increased in the fetal bloodstream, and CMV neutralizing titers in maternal and fetal blood were comparable. Conclusions: CMV-specific, high-avidity neutralizing antibodies from maternal circulation are transcytosed to the fetal bloodstream, contribute to suppression of viral replication in the placenta and could prevent congenital disease. (c) 2009 Elsevier B.V. All rights reserved.