Pathogenesis of congenital cytomegalovirus infection : finding prognostic markers and correlates of protection

Cytomegalovirus (CMV) infection is a worldwide common infection that in a considerable proportion of individuals remains unnoticed. The congenital CMV infection (cCMV) can induce a variety of clinical manifestations at birth (symptoms at birth), and of permanent long-term impairments (LTI). Of the total of infected neonates at birth, 13% are symptomatic at birth, and half of them will develop LTI. However, 13% of the asymptomatic neonates will still develop the same LTI. Therefore, a quite high percentage of neonates will develop LTI. This thesis aimed to identify prognostic markers, for short- and long-term clinical outcome, and correlates of protection, for future vaccine development. In order to identify such biomarkers, a retrospective nationwide cohort of children with (n=125) and without (n=263) cCMV was used. The findings of this thesis allowed us to get more insights into cCMV pathogenesis, and into the potential processes leading to immune dysfunction, and therefore to a worse clinical outcome. Several approaches have been used to explore prognostic markers. The neonatal immune markers, through DNA quantification of the most common TCR and BCR rearrangements from DBS, together with the maternal-child HLA background, through typing DNA from buccal swabs, seemed to be quite promising for prognostic markers.