Low interferon relative-response to cytomegalovirus is associated with low likelihood of intrauterine transmission of the virus

Abstract

Background Congenital 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 Aim To establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response. Methods We analyzed IFN-Γ secretion upon whole blood stimulation from primary CMV-infected pregnant women, with either CMV-peptides or PHA-mitogen. Results We 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.Conclusion In pregnant women with primary CMV infection, low IFN-Γ RR is associated with low risk of transmission.