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Front Immunol. 2018 May 9;9:993. doi: 10.3389/fimmu.2018.00993. eCollection 2018.

Meta-Analysis of Maternal and Fetal Transcriptomic Data Elucidates the Role of Adaptive and Innate Immunity in Preterm Birth.

Author information

1
Institute for Computational Health Sciences, University of California San Francisco, San Francisco, CA, United States.
2
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, United States.
3
Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, United States.
4
Department of Pediatrics, University of California San Francisco, San Francisco, CA, United States.
5
Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, CA, United States.
6
Department of Surgery, University of California San Francisco, San Francisco, CA, United States.

Abstract

Preterm birth (PTB) is the leading cause of newborn deaths around the world. Spontaneous preterm birth (sPTB) accounts for two-thirds of all PTBs; however, there remains an unmet need of detecting and preventing sPTB. Although the dysregulation of the immune system has been implicated in various studies, small sizes and irreproducibility of results have limited identification of its role. Here, we present a cross-study meta-analysis to evaluate genome-wide differential gene expression signals in sPTB. A comprehensive search of the NIH genomic database for studies related to sPTB with maternal whole blood samples resulted in data from three separate studies consisting of 339 samples. After aggregating and normalizing these transcriptomic datasets and performing a meta-analysis, we identified 210 genes that were differentially expressed in sPTB relative to term birth. These genes were enriched in immune-related pathways, showing upregulation of innate immunity and downregulation of adaptive immunity in women who delivered preterm. An additional analysis found several of these differentially expressed at mid-gestation, suggesting their potential to be clinically relevant biomarkers. Furthermore, a complementary analysis identified 473 genes differentially expressed in preterm cord blood samples. However, these genes demonstrated downregulation of the innate immune system, a stark contrast to findings using maternal blood samples. These immune-related findings were further confirmed by cell deconvolution as well as upstream transcription and cytokine regulation analyses. Overall, this study identified a strong immune signature related to sPTB as well as several potential biomarkers that could be translated to clinical use.

KEYWORDS:

immunology; meta-analysis; pregnancy; preterm birth; transcriptomics

PMID:
29867970
PMCID:
PMC5954243
DOI:
10.3389/fimmu.2018.00993
[Indexed for MEDLINE]
Free PMC Article

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