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NEWBORNS WITH ZIKA VIRUS-ASSOCIATED MICROCEPHALY EXHIBIT MARKED SYSTEMIC INFLAMMATORY IMBALANCE (PREPRINT)
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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.
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