PMID- 34159362 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20220103 IS - 1529-7268 (Electronic) IS - 0006-3363 (Linking) VI - 105 IP - 4 DP - 2021 Oct 11 TI - Evidence for a shift in placental HLA-G allelic dominance and the HLA-G isoform profile during a healthy pregnancy and preeclampsiadagger. PG - 846-858 LID - 10.1093/biolre/ioab121 [doi] AB - 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. CI - (c) 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. FAU - Persson, Gry AU - Persson G AD - Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital, Roskilde, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark. FAU - Staehr, Christina Seefeldt AU - Staehr CS AD - Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital, Roskilde, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark. FAU - Klok, Freja Syrach AU - Klok FS AD - Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital, Roskilde, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark. FAU - Lebech, Morten AU - Lebech M AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark. AD - Department of Gynaecology and Obstetrics, Zealand University Hospital, Roskilde, Denmark. FAU - Hviid, Thomas Vauvert F AU - Hviid TVF AD - Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital, Roskilde, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (HLA-G Antigens) RN - 0 (Protein Isoforms) SB - IM MH - Adult MH - Female MH - Gene Expression Profiling MH - HLA-G Antigens/*genetics/metabolism MH - Humans MH - Pilot Projects MH - *Polymorphism, Genetic MH - Pre-Eclampsia/*genetics/metabolism MH - Pregnancy/*metabolism MH - Protein Isoforms OTO - NOTNLM OT - HLA-G OT - allele OT - isoform OT - preeclampsia OT - pregnancy OT - reproductive immunology EDAT- 2021/06/24 06:00 MHDA- 2022/01/04 06:00 CRDT- 2021/06/23 07:25 PHST- 2021/03/17 00:00 [received] PHST- 2021/06/08 00:00 [revised] PHST- 2021/06/15 00:00 [accepted] PHST- 2021/06/24 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] PHST- 2021/06/23 07:25 [entrez] AID - 6307734 [pii] AID - 10.1093/biolre/ioab121 [doi] PST - ppublish SO - Biol Reprod. 2021 Oct 11;105(4):846-858. doi: 10.1093/biolre/ioab121.