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Protein Profiles Could ID Zika-Infected Pregnant Women at High Risk of Abnormal Births

NEW YORK (GenomeWeb) – A team led by researchers at the University of Southern California's Keck School of Medicine has identified altered immune protein expression patterns in pregnant women infected with Zika virus.

According to the scientists, these patterns could be useful as biomarkers for identifying pregnant women likely to have been infected with Zia whose babies may be at risk of developing Zika-linked abnormalities.

The results were presented in a study published last week in JCI Insight by a team led by senior author Jae Jung, professor of molecular microbiology and immunology at the Keck School of Medicine.

Zika infections in pregnant women have been linked to a variety of birth defects including microcephaly. However, as the JCI authors noted, the mechanisms by which Zika leads to these birth defects remains poorly understood.

To gain insights into the links between Zika pathogenesis and birth defects, the researchers profiled the immune response of Zika infected women and healthy controls, measuring the levels of 69 cytokines in the serum from 74 women — 30 healthy pregnant Brazilian controls, 30 pregnant Brazilian women infected with Zika, and 14 healthy pregnant controls from Los Angeles. In the infected group Zika-positive subjects were recruited based on the presence of a rash and confirmed using qPCR.

Upon follow-up, 50 percent of infected women had normal births, 6.7 percent had miscarriages, 16.7 percent had pre-term births, and 25 percent had birth abnormalities.

Looking at the cytokine profiles of the infected women, the researcher found that 45 of the 69 proteins measured were dysregulated in women with Zika compared to healthy controls, with 24 of those proteins upregulated, and the proinflammatory cytokine CXCL10 the most highly upregulated protein in Zika infected women.

Based on the cytokine dysregulation observed, the authors hypothesized that "the ZIKV-induced cytokine milieu during pregnancy may result in infiltration of leukocyte, particularly monocytes and NK cells, which ultimately contributes to viral pathogenesis."

They noted that this would fit with "growing evidence" of "the negative impact of inflammation on fetal neurodevelopment, suggesting that ZIKV-mediated immunomodulatory strategy during pregnancy may be the underlying cause of abnormal birth outcomes."

The researchers also compared the cytokine profiles of the 15 Zika infected women with normal outcomes to the 15 infected women with abnormal outcomes and identified increased expression of 16 inflammatory cytokines in the latter group, including a pattern in which the cytokine CCLP was expressed in inverse proportion to CD163, TNFRSF1A and CCL22 in women with abnormal births.

"This suggests that the CCL2 level and its inverse relationship with CD163, TNFRSF1A, and CCL22 may serve as potential biomarkers to predict ZIKV-associated fetal abnormalities," the authors wrote, indicating that cytokine profiling could allow for distinguishing between Zika infected women at low and high risk of having abnormal births.