Cytokine Profiling of Amniotic Fluid from Congenital Cytomegalovirus Infection
Nicolas Bourgon,
Wendy Fitzgerald,
Hugues Aschard,
Jean-François Magny,
Tiffany Guilleminot,
Julien Stirnemann,
Roberto Romero,
Yves Ville,
Leonid Margolis,
Marianne Leruez-Ville
Affiliations
Nicolas Bourgon
Service d’Obstétrique—Maternité, Chirurgie, Médecine et Imagerie Fœtales, Hôpital Necker Enfants Malades, GHU Paris Centre, AP-HP, F-75015 Paris, France
Wendy Fitzgerald
Section of Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA
Hugues Aschard
Department of Computational Biology, Institut Pasteur, Université Paris Cité, F-75015 Paris, France
Jean-François Magny
Équipe d’Accueil «FŒTUS» 73-28, Université Paris Cité, F-75015 Paris, France
Tiffany Guilleminot
Équipe d’Accueil «FŒTUS» 73-28, Université Paris Cité, F-75015 Paris, France
Julien Stirnemann
Service d’Obstétrique—Maternité, Chirurgie, Médecine et Imagerie Fœtales, Hôpital Necker Enfants Malades, GHU Paris Centre, AP-HP, F-75015 Paris, France
Roberto Romero
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA
Yves Ville
Service d’Obstétrique—Maternité, Chirurgie, Médecine et Imagerie Fœtales, Hôpital Necker Enfants Malades, GHU Paris Centre, AP-HP, F-75015 Paris, France
Leonid Margolis
Section of Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA
Marianne Leruez-Ville
Équipe d’Accueil «FŒTUS» 73-28, Université Paris Cité, F-75015 Paris, France
Background: Congenital cytomegalovirus (cCMV) infection is frequent and potentially severe. The immunobiology of cCMV infection is poorly understood, involving cytokines that could be carried within or on the surface of extracellular vesicles (EV). We investigated intra-amniotic cytokines, mediated or not by EV, in cCMV infection. Methods: Forty infected fetuses following early maternal primary infection and forty negative controls were included. Infected fetuses were classified according to severity at birth: asymptomatic, moderately or severely symptomatic. Following the capture of EV in amniotic fluid (AF), the concentrations of 38 cytokines were quantified. The association with infection and its severity was determined using univariate and multivariate analysis. A prediction analysis based on principal component analysis was conducted. Results: cCMV infection was nominally associated with an increase in six cytokines, mainly soluble (IP-10, IL-18, ITAC, and TRAIL). EV-associated IP-10 was also increased in cases of fetal infection. Severity of fetal infection was nominally associated with an increase in twelve cytokines, including five also associated with fetal infection. A pattern of specific increase in six proteins fitted severely symptomatic infection, including IL-18soluble, TRAILsoluble, CRPsoluble, TRAILsurface, MIGinternal, and RANTESinternal. Conclusion: Fetal infection and its severity are associated with an increase in pro-inflammatory cytokines involved in Th1 immune response.
