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

EBioMedicine
Satu WedenojaJuha Kere

Abstract

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. 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 (IFNα) protein expression by immunohistochemistry. 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. 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. Finnish Medical Founda...Continue Reading

Associated Datasets

Citations

Nov 26, 2020·British Journal of Biomedical Science·M HaghiM A Hosseinpour-Feizi
Dec 1, 2020·Journal of Reproductive Immunology·Daniel P JacobsenAnne Cathrine Staff
Apr 7, 2021·Human Immunology·A Inkeri Lokki, Jenni Heikkinen-Eloranta
Apr 14, 2021·Journal of Leukocyte Biology·Derek MillerNardhy Gomez-Lopez
May 30, 2021·HLA : Immune Response Genetics·Tuomas KaprioSatu Wedenoja

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Datasets Mentioned

BETA
GSE125460
U13369

Methods Mentioned

BETA
PCR
biopsy
biopsies
ELISA
Assay
RNA-seq

Key Resources (RRID) Mentioned

SCR_006828
SCR_018052
SCR_018042
SCR_018043
SCR_018095
SCR_002678
SCR_014983
SCR_005012
SCR_015058
SCR_015687

Software Mentioned

GraphPad Prism
Ensembl
MultiQC
HISAT2
IlluminaBasecallsToSam
featureCounts
DESeq2
Aiforia Create
ER Mapper
Gen5

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