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

Abstract

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.

Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring

“…Maternal blood levels of these cytokines were lower in the ZIKV group (although the difference was not statistically significant) ( S2 Fig ) that could potentially contribute to the lower cytokine levels in offspring. Previously described markers of maternal immune activation which may affect fetal health, IL-6 [43] and IL-17A [44] in the ZIKV group were lower or equal to that in control litters ( P ≥ 0.47); these data are in agreement with findings in pregnant women with acute ZIKV infection [45] and mice [12]. Also, IL-6 and IL-17A levels in ZIKV group did not change significantly throughout the experiment ( S2 Fig ); the same was found for maternal IL-1 β , IL-8, IL-10, IL-12, IL-13, IFN- β , and IFN-γ ( S2 Fig ).…”

“…To our knowledge, type I IFN profiles in human fetuses and offspring affected with ZIKV infection were not addressed, yet. However, it has been shown that acute ZIKV infection is associated with increased IFN-α levels in the blood sera of pregnant women [45]. Human infections with other related flaviviruses (dengue virus and West Nile virus) were also associated with increased IFN-α levels in the blood plasma/sera [86,87].…”

Host Immune Response to ZIKV in an Immunocompetent Embryonic Mouse Model of Intravaginal Infection

“…Corroborating these results, it has been shown that CCL2 levels were found to be increased in the amniotic fluid of ZIKV-positive women giving birth to babies with neonatal microcephaly, relative to uninfected control group [50]. Similarly, CXCL10, a chemokine that has been associated with neuronal damage, was the most highly induced inflammatory factor in symptomatic ZIKV-positive pregnant women and was also specifically elevated in pregnant women with abnormal birth outcomes [49,51]. Therefore, the elevated levels of these chemokines could be playing a detrimental role in ZIKV-infected embryo brains.…”

“…Increased transcriptional levels of the chemokines CCL2, CXCL1 and CXCL10 in the brain of ZIKV-positive embryos could indicate the increased recruitment of inflammatory cells, facilitating viral elimination, but also exacerbating neuroinflammation. Interestingly, it has been shown that CCL2 levels are increased in ZIKV-infected pregnant women [49]. Notably, CCL2 was found to be the most highly induced inflammatory factor in ZIKV-positive pregnant women with abnormal birth outcomes, as compared to that of ZIKV-positive pregnant women without birth complications [49].…”

“…Interestingly, it has been shown that CCL2 levels are increased in ZIKV-infected pregnant women [49]. Notably, CCL2 was found to be the most highly induced inflammatory factor in ZIKV-positive pregnant women with abnormal birth outcomes, as compared to that of ZIKV-positive pregnant women without birth complications [49]. Corroborating these results, it has been shown that CCL2 levels were found to be increased in the amniotic fluid of ZIKV-positive women giving birth to babies with neonatal microcephaly, relative to uninfected control group [50].…”