Biomarkers and immunoprofiles associated with fetal abnormalities of ZIKV-positive pregnancies.

BACKGROUND: An intricate fetal-maternal immune crosstalk during pregnancy is essential for a healthy birth. Hence, the infection-induced alterations of maternal immunity often lead to adverse outcomes for mother and/or child. The emergence of Zika virus (ZIKV) infection in pregnant women has been associated with more than 3,000 cases of microcephaly and nervous system malformations.

METHODS: To explore the potential correlation of ZIKV-induced alteration of maternal immunity with fetal abnormalities, we performed extensive sera immunoprofiling of 74 pregnant women: 30 symptomatic ZIKV+ pregnant patients and 30 healthy pregnant controls in ZIKV-endemic Rio de Janeiro, along with 14 healthy pregnant controls in non-endemic Los Angeles.

RESULTS: Extensive multiplexing analysis of 69 cytokines revealed that CXCL10, CCL2, and CCL8 chemokines were specifically associated with symptomatic ZIKV+ infection during pregnancy, and distinct immunoprofiles were detected at different trimesters in ZIKV-infected pregnant women. Intriguingly, the high CCL2 level and its inverse correlation with CD163, TNFRSF1A, and CCL22 levels was apparently associated with ZIKV-induced abnormal birth.

CONCLUSION: Our findings provide insights into the alteration of ZIKV-elicited maternal immunity, serving as a potential clinical biomarker platform.

FUNDING: NIH (CA200422, CA180779, DE023926, AI073099, AI116585, AI129496, AI140705, AI069120, AI056154, AI078389, AI28697, AI40718 and AI129534-01), Hastings Foundation, Fletcher Jones Foundation, Departamento de Ciência e Tecnologia (DECIT/25000.072811/2016-17) do Ministério da Saúde do Brasil, and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior CAPES/88887.116627/2016-01.