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JCI Insight. 2018 Nov 2;3(21). pii: 124152. doi: 10.1172/jci.insight.124152.

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

Author information

1
Department of Molecular Microbiology and Immunology and.
2
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Zilkha Neurogenetic Institute, Los Angeles, California, USA.
3
Institute for Glycomics, Griffith University, Gold Coast, Southport, Queensland, Australia.
4
Department of Microbiology and Molecular Genetics and.
5
Division of Pediatric Infectious Diseases, David Geffen School of Medicine, UCLA, Marion Davies Children's Health Center, Los Angeles, California, USA.
6
Laboratório de Pesquisa Clínica em Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fondação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.

Abstract

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.

KEYWORDS:

Chemokines; Cytokines; Infectious disease; Reproductive Biology

PMID:
30385728
PMCID:
PMC6238739
DOI:
10.1172/jci.insight.124152
[Indexed for MEDLINE]
Free PMC Article

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