Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream
Received 8 July 2009; received in revised form 7 October 2009; accepted 7 October 2009. published online 26 October 2009.
Abstract
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.
Department of Cell and Tissue Biology, School of Dentistry, University of California–San Francisco, San Francisco, CA 94122, United States
Corresponding author at: C734, Box 0640, University of California–San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, United States. Tel.: +1 415 476 8248; fax: +1 415 476 3983.
ABSTRACT