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

JCI Insight. 2018 Nov 2;3(21):e124152. doi: 10.1172/jci.insight.124152.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Biomarkers / metabolism*
  • Brazil / epidemiology
  • Cytokines / blood
  • Cytokines / metabolism
  • Female
  • Fetus / abnormalities*
  • Fetus / metabolism
  • Fetus / virology
  • Healthy Volunteers
  • Humans
  • Immunity, Maternally-Acquired / physiology
  • Microcephaly / epidemiology
  • Microcephaly / etiology*
  • Pregnancy
  • Pregnancy Outcome / epidemiology
  • Pregnancy Trimesters
  • United States / epidemiology
  • Young Adult
  • Zika Virus / immunology*
  • Zika Virus Infection / complications
  • Zika Virus Infection / epidemiology
  • Zika Virus Infection / metabolism*

Substances

  • Biomarkers
  • Cytokines