Congenital Cytomegalovirus Conference - Congenital CMV ...

Results: CMV pp65-specific CD4+ or CD8+ T cell responses were detected in 3 of 4 infants studied at
frequencies of 0.03 - 0.5% of CD4+ or CD8+ T cells. In all 3 infants, CMV-specific T cells expressed 1 or 2
functions, but the pattern of responses differed between infants. In a mother-infant pair, responses against
pp65 were detectable by single- or bi-functional CD107a/b, MIP-1β, TNF-α, and IFN-γ (not IL2) expression
by both CD4+ and CD8+ T cells in the mother at 27 weeks gestation (9 weeks after onset of primary
CMV infection), but only by CD8+ T cells in her infant at 2 days of age. No functional CMV-specific CD4+
T cells were detectable in the infant.
Conclusions: Preliminary results suggest that in infants with congenital CMV infection, patterns of CMVspecific
T cell effector function may vary, polyfunctional T cells are detectable, and the functionality of
some T cell subsets may be reduced compared to adults. Studies further characterizing T cell responses to
CMV pp65 or IE-2 proteins are ongoing for the remainder of the study cohort.
O-16 Congenital CMV Infection is Associated with Angiogenic Imbalance in the Placenta.
Ekaterina Maidji, Nigro, G., Muci, S., Aziz, N., Shiboski S., Lenore Pereira. Department of Cell and Tissue
Biology University of California, San Francisco, CA.
Background: Human cytomegalovirus (CMV) is a leading cause of congenital viral infection accounting
1-3% of all live births in the US. Different strategies - evaluation of maternal humoral immunity and
detection of viral DNA in amniotic fluid - have been used for prenatal diagnosis of congenital infection.
Availability of preventative treatment provides a solid rational for development of early biomarkers.
Objectives: Detailed immmunohistological analysis of congenitally infected placentas with and without
hyperimmune globulin (HIG) treatment (Nigro et al., NEJM 2005) showed that untreated infection injures
the uterine vasculature and fetal capillaries that could restrict blood flow causing local hypoxia. Up-regulation
of hypoxia-inducible factors, vascular endothelial growth factor (VEGF) and its inhibitory receptor
soluble Flt1 (sFlt1) in congenitally infected placentas suggested circulating factors could serve as supplementary
evidence of viral replication in specialized cells of the placenta.
Methods: Amniotic fluid (57 samples) from 3 groups was studied: CMV infected-HIG-treated prevention,
infected untreated, and healthy seronegative controls. Concentrations of sFlt1, VEGF bound to sFlt1
(bVEGF), “free” VEGF (active form), and placental growth factor (PlGF) were measured using commercial
ELISA kits (R&D System and Chemicon International).
Results: Amniotic fluid from congenital infection contained exceptionally high levels of sFlt1 and bVEGF,
but little PlGF and no free VEGF. In the HIG-treated prevention group, sFlt1 and bVEGF levels were
sharply reduced, and PlGF was unchanged. In addition, the anti-angiogenic index (sFlt1/PlGF) was significantly
elevated in amniotic fluid in all congenital infection as compared with the healthy control group
(P