Evidence for a shift in placental HLA-G allelic dominance and the HLA-G isoform profile during a healthy pregnancy and pre-eclampsia

Gry Persson, Christina Seefeldt Stæhr, Freja Syrach Klok, Morten Lebech, Thomas Vauvert F Hviid*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelpeer review

Abstrakt

Human leukocyte antigen (HLA)-G, which belongs to a nonclassical class Ib major histocompatibility complex gene family expressed by placental trophoblast cells, plays a central role in establishing tolerance to the semiallogeneic fetus and in placentation. HLA-G exists in different soluble or membrane-bound isoforms. Preeclampsia, a major cause of fetal and maternal morbidity and mortality, has been linked to insufficient placentation and an altered immune response in pregnancy, including altered HLA-G expression. The 14 bp insertion/deletion polymorphism in the 3' untranslated region of the gene and the isoform profile may affect HLA-G expression. The aim of the current pilot study was to characterize the expression patterns of HLAG mRNA, protein, and isoform profile in uncomplicated term pregnancies and in cases of preeclampsia. Maternal sHLA-G mRNA and protein levels were slightly reduced in preeclampsia. No difference was found for placental blood, and no correlation between peripheral and placental sHLA-G levels was found. We observed no association between neither fetal nor maternal HLA-G 14 bp insertion/deletion genotypes and preeclampsia, nor a significant difference in isoform profiles. However, in HLA-G 14 bp insertion/deletion heterozygous placental samples, we observed abundant HLA-G1 14 bp insertion allele expression in the term placentae, which is contrary to previous findings in first trimester trophoblast. Increased HLA-G1 14 bp insertion allele expression in the placenta was associated with reduced levels of placental sHLA-G and an altered isoform profile with increased relative levels of HLA-G1 and -G5 and reduced levels of HLA-G3. The results indicate that an allelic shift in heterozygous individuals could represent a novel regulatory pathway.

OriginalsprogEngelsk
Sider (fra-til)846-858
Antal sider13
TidsskriftBiology of Reproduction
Vol/bind105
Udgave nummer4
Tidlig onlinedato22 jun. 2021
DOI
StatusUdgivet - 11 okt. 2021

Bibliografisk note

© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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