Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia

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Wedenoja , S , Yoshihara , M , Teder , H , Sariola , H , Gissler , M , Katayama , S , Wedenoja , J , Häkkinen , I M K , Ezer , S , Linder , N , Lundin , J , Skoog , T , Sahlin , E , Iwarsson , E , Pettersson , K , Kajantie , E , Mokkonen , M , Heinonen , S , Laivuori , H , Krjutskov , K & Kere , J 2020 , ' Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia ' , EBioMedicine , vol. 59 , 102872 . https://doi.org/10.1016/j.ebiom.2020.102872

Title: Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
Author: Wedenoja, Satu; Yoshihara, Masahito; Teder, Hindrek; Sariola, Hannu; Gissler, Mika; Katayama, Shintaro; Wedenoja, Juho; Häkkinen, Inka M. K.; Ezer, Sini; Linder, Nina; Lundin, Johan; Skoog, Tiina; Sahlin, Ellika; Iwarsson, Erik; Pettersson, Karin; Kajantie, Eero; Mokkonen, Mikael; Heinonen, Seppo; Laivuori, Hannele; Krjutskov, Kaarel; Kere, Juha
Contributor: University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, Helsinki One Health (HOH)
University of Helsinki, Clinicum
University of Helsinki, Faculty of Medicine
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Medicum
University of Helsinki, Johan Edvard Lundin / Principal Investigator
University of Helsinki, HUS Children and Adolescents
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
Date: 2020-09
Language: eng
Number of pages: 13
Belongs to series: EBioMedicine
ISSN: 2352-3964
URI: http://hdl.handle.net/10138/320560
Abstract: Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses. Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFN alpha) protein expression by immunohistochemistry. Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas. Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials. (C) 2020 The Authors. Published by Elsevier B.V.
Subject: 3' UNTRANSLATED REGION
BALANCING SELECTION
Balancing selection
EXTRAVILLOUS TROPHOBLASTS
GENE-EXPRESSION
HLA-G
I INTERFERONS
Interferon alpha
MATERNAL CIRCULATION
PREGNANCY
Preeclampsia
SELECTIVE ADVANTAGE
SEX-RATIO
SINGLE-CELL TRANSCRIPTOME
Sex ratio
Stillbirth
3121 Internal medicine
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