Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells

S. Djurisic, S. Teiblum, C. K. Tolstrup, O. B. Christiansen, T. V.F. Hviid

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3′-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specificmRNAtranscripts, which was further associated with lowlevels ofHLA-Gsurface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and singlenucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNAalleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications.

OriginalsprogEngelsk
Sider (fra-til)281-295
Antal sider15
TidsskriftMolecular Human Reproduction
Vol/bind21
Udgave nummer3
DOI
StatusUdgivet - 23 sep. 2014

Fingeraftryk Udforsk hvilke forskningsemner 'Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells' indeholder.

Citationsformater