Research on Zika biomarker detection and prenatal diagnosis

Biomarker detection plays a very important role in disease diagnosis and drug treatment effect monitoring.

The Zika virus was identified in the late 1940s in Africa but was first confirmed in Brazil in May 2015, it's a member of the Flaviviridae family, genus Flavivirus, which includes dengue, yellow fever, and West Nile viruses.

Zika virus is an arbovirus (arthropod-borne virus), that causes either a mild illness with fever, rash, conjunctivitis, arthralgia, and myalgia, or it may be subclinical

Investigators at USC believe that after immunoprofiling a number of symptomatic Zika virus positive (ZIKV⁺) pregnant patients and extensive multiplexing analysis of their cytokine levels that they have identified a panel of biomarkers that are “specifically associated with symptomatic ZIKV⁺ infection during pregnancy.” This is an important discovery that could lead to screening tests and a better understanding about how the infection leads to fetal abnormalities. Findings from the new study were published in the Journal of Clinical Investigation Insight through an article titled “Biomarkers and immunoprofiles associated with fetal abnormalities of ZIKV-positive pregnancies.”

“The highest risk of birth defects is from Zika virus infection during the first and second trimester. A prenatal test has the potential to relieve the concerns of many expectant mothers,” explained lead study investigator Suan-Sin Foo, Ph.D., a research associate in the department of molecular microbiology and immunology at the Keck School of Medicine of USC. “We still have a lot to learn about how the Zika virus affects the immune responses in the mother, and how infection can negatively impact her baby.”

Zika virus, which is spread by Aedes aegypti mosquitoes, typically does not affect most of those it infects – low-grade fever being the most noticeable symptom. However, fetuses exposed to Zika in the womb are at risk for devastating neurological defects. One of those defects, microcephaly – a smaller-than-usual head size – gained prominence in 2015 with Brazil reporting an unusual number of cases in babies born to mothers infected with the virus.

Sadly, as those infants have become toddlers, many can’t see, walk, chew, or talk and will require a lifetime of care, according to the U.S. Centers for Disease Control and Prevention. In the U.S., there have been approximately 2,483 pregnant women infected with Zika and 116 infants born with Zika-associated birth defects since 2015.

In the current study, the researchers examined the immune systems of pregnant women through blood samples taken during the first, second, and third trimesters of pregnancy. They compared blood samples from 30 Zika-infected, pregnant women in Brazil with 30 healthy pregnant women in Brazil and 14 in Los Angeles.

Specifically, the researchers were looking at cytokines, which are messenger chemicals released by the body in response to an infection. Across a panel of 69 cytokines screened, they identified 16 cytokines that appeared to be associated with Zika-induced abnormal births.

“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,” the authors wrote. “Intriguingly, the high CCL2 level and its inverse correlation with CD163, TNFRSF1A, and CCL22 levels were apparently associated with ZIKV-induced abnormal birth.”

At the moment, the research team isn’t sure whether the messenger chemicals cause the birth defects or are secreted in response to something else.

“Ultrasound is routinely used during pregnancy to check a baby’s condition, but there’s a limit to what can be seen. Magnetic resonance imaging can give clear, high-resolution ‘snapshots’ of the fetus, but there are safety concerns for the baby, and it is recommended for second- and third-trimester pregnancy,” concluded co-lead study investigator Weiqiang Chen, Ph.D., a research associate in the department of molecular microbiology and immunology at the Keck School of Medicine. “Our findings identified a panel of biomarkers which may potentially be useful in predicting Zika-associated fetal outcomes regardless of pregnancy stages, simply by evaluating the mothers’ blood.”

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