Abstract
BackgroundCongenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe mental and hearing impairments. Notably, only 40% of primarily infected women transmit CMV to the fetus. CMV-specific T-cell response has a role in CMV disease but individual immune heterogeneity precludes reliable correlation between measurable T-cells response and intrauterine transmission.Study AimTo establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response.MethodsWe analyzed IFN-γ secretion upon whole blood stimulation from primary CMV-infected pregnant women, with either CMV-peptides or PHA-mitogen.ResultsWe established a new normalization method of individual IFN-γ response to CMV by defining the ratio between specific-CMV response and non-specific mitogen response (defined as IFN-γ relative response, RR), aiming to overcome high person-to-person immune variability. We found a unique subpopulation of women with low IFN-γ RR strongly correlated with absence of transmission. IFN-γ RR lower than 1.8% (threshold determined by ROC analysis) reduces the pre-test probability of transmission from 40% to 8%, revealing an unexpected link between low IFN-γ RR and non-transmission.ConclusionIn pregnant women with primary CMV infection, low IFN-γ RR is associated with low risk of transmission.
Highlights
Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world, affecting 0.5–2% of all live births in the United States and Europe [1,2,3,4]
IFN-γ relative response' (RR) lower than 1.8% reduces the pre-test probability of transmission from 40% to 8%, revealing an unexpected link between low IFN-γ RR and non-transmission
Pregnant women with primary CMV infection and IFN-γ RR
Summary
Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world, affecting 0.5–2% of all live births in the United States and Europe [1,2,3,4]. Fetal CMV infection can cause a variety of long-term disabilities including mental, hearing and visual impairments [5,6,7]. Severe disabilities caused by congenital CMV infection threaten more children than several well-known childhood maladies such as Down's syndrome or fetal alcohol syndrome [4, 8]. Congenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe mental and hearing impairments. Study Aim. To establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response
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