A1 Refereed original research article in a scientific journal
Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
Authors: Satu Wedenoja, Masahito Yoshihara, Hindrek Tederd, Hannu Sariola, Mika Gissler, Shintaro Katayama, Juho Wedenoja, Inka M. Häkkinen, Sini Ezer, Nina Linder, Johan Lundin, Tiina Skoog, Ellika Sahlin, Erik Iwarsson, Karin Pettersson, Eero Kajantie, Mikael Mokkonen, Seppo Heinonen, Hannele Laivuori, Kaarel Krjutškov, Juha Kere
Publisher: ELSEVIER
Publication year: 2020
Journal: EBioMedicine
Journal name in source: EBIOMEDICINE
Journal acronym: EBIOMEDICINE
Article number: ARTN 102872
Volume: 59
Number of pages: 13
ISSN: 2352-3964
eISSN: 2352-3964
DOI: https://doi.org/10.1016/j.ebiom.2020.102872
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/50693765
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.
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