Newborns with Zika virus-associated microcephaly exhibit marked systemic inflammatory imbalance.

BACKGROUND: Zika Virus (ZIKV) is an emergent flavivirus initially considered a benign and self-limited exanthematic illness. In 2015, a new epidemic emerged in northeastern of Brazil with increased incidence of a previously rare clinical outcome, microcephaly, in newborns from mothers who were infected during pregnancy. Little is known about the immunopathogenesis of ZIKV-associated microcephaly. Understanding the inflammatory profile and degree of inflammation of persons affected with such condition is an important step towards development of innovative therapeutic strategies. METHODS: A case-control study compared plasma levels of several inflammatory biomarkers from newborns with ZIKV-microcephaly, asymptomatic ZKV infection or uninfected controls. Plasma biomarkers were assessed using Luminex. A series of multidimensional analysis was performed to characterize the systemic immune activation profile of the clinical groups. RESULTS: We identified an inflammatory signature associated with ZIKV-microcephaly that suggested an increased inflammation. Network analysis suggested that ZIKV-microcephaly is associated with imbalanced immune activation and inflammation. The cephalic perimeter was inversely proportional with the degree of inflammatory perturbation. Furthermore, a combination of plasma inflammatory biomarkers could discriminate ZIKV with microcephaly from those with ZIKV without microcephaly or uninfected neonates. CONCLUSIONS: An intense inflammatory imbalance which is proportional to the disease severity hallmarks ZIKV-microcephaly.