PMID- 30717132 OWN - NLM STAT- MEDLINE DCOM- 20190517 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 3 DP - 2019 Feb 1 TI - Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels. LID - 10.3390/ijms20030625 [doi] LID - 625 AB - Human leukocyte antigen (HLA)-G is an immune modulating molecule that is present on fetal extravillous trophoblasts at the fetal-maternal interface. Single nucleotide polymorphisms (SNPs) in the 3 prime untranslated region (3'UTR) of the HLA-G gene can affect the level of HLA-G expression, which may be altered in women with recurrent miscarriages (RM). This case-control study included 23 women with a medical history of three or more consecutive miscarriages who delivered a child after uncomplicated pregnancy, and 46 controls with uncomplicated pregnancy. Genomic DNA was isolated to sequence the 3'UTR of HLA-G. Tissue from term placentas was processed to quantify the HLA-G protein and mRNA levels. The women with a history of RM had a lower frequency of the HLA-G 3'UTR 14-bp del/del genotype as compared to controls (Odds ratio (OR) 0.28; p = 0.039), which has previously been related to higher soluble HLA-G levels. Yet, HLA-G protein (OR 6.67; p = 0.006) and mRNA (OR 6.33; p = 0.010) expression was increased in term placentas of women with a history of RM as compared to controls. In conclusion, during a successful pregnancy, HLA-G expression is elevated in term placentas from women with a history of RM as compared to controls, despite a genetic predisposition that is associated with decreased HLA-G levels. These findings suggest that HLA-G upregulation could be a compensatory mechanism in the occurrence of RM to achieve an ongoing pregnancy. FAU - Craenmehr, Moniek H C AU - Craenmehr MHC AUID- ORCID: 0000-0001-5505-8195 AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. m.h.c.craenmehr@lumc.nl. FAU - Nederlof, Iris AU - Nederlof I AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. iris.nederlof@xs4all.nl. FAU - Cao, Milo AU - Cao M AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. milocao@outlook.com. FAU - Drabbels, Jos J M AU - Drabbels JJM AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. J.J.M.Drabbels@lumc.nl. FAU - Spruyt-Gerritse, Marijke J AU - Spruyt-Gerritse MJ AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. M.J.Spruyt-Gerritse@lumc.nl. FAU - Anholts, Jacqueline D H AU - Anholts JDH AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. J.D.H.Anholts@lumc.nl. FAU - Kapsenberg, Hanneke M AU - Kapsenberg HM AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. J.M.Kapsenberg@lumc.nl. FAU - Stegehuis, Janine A AU - Stegehuis JA AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. J.A.Stegehuis-Kamp@lumc.nl. FAU - van der Keur, Carin AU - van der Keur C AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. C.van_der_Keur@lumc.nl. FAU - Fasse, Esther AU - Fasse E AD - Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. Esther.Fasse@radboudumc.nl. FAU - Haasnoot, Geert W AU - Haasnoot GW AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. G.W.Haasnoot@lumc.nl. FAU - van der Hoorn, Marie-Louise P AU - van der Hoorn MP AD - Department of Obstetrics and Gynaecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. M.L.P.van_der_Hoorn@lumc.nl. FAU - Claas, Frans H J AU - Claas FHJ AUID- ORCID: 0000-0003-4157-6201 AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. F.H.J.Claas@lumc.nl. FAU - Heidt, Sebastiaan AU - Heidt S AUID- ORCID: 0000-0002-6700-188X AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. S.Heidt@lumc.nl. FAU - Eikmans, Michael AU - Eikmans M AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. M.Eikmans@lumc.nl. LA - eng PT - Journal Article DEP - 20190201 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (3' Untranslated Regions) RN - 0 (HLA-G Antigens) SB - IM MH - 3' Untranslated Regions MH - Abortion, Habitual/*genetics/immunology/metabolism/physiopathology MH - Adult MH - Case-Control Studies MH - Female MH - Gene Expression MH - Gravidity/immunology MH - HLA-G Antigens/*genetics/immunology MH - Humans MH - Parity/immunology MH - Placenta/immunology/*metabolism MH - *Polymorphism, Single Nucleotide MH - Pregnancy MH - Trophoblasts/immunology/*metabolism PMC - PMC6387365 OTO - NOTNLM OT - HLA-G OT - immunohistochemistry OT - placenta OT - pregnancy OT - recurrent miscarriage COIS- The authors declare no conflict of interest. EDAT- 2019/02/06 06:00 MHDA- 2019/05/18 06:00 PMCR- 2019/02/01 CRDT- 2019/02/06 06:00 PHST- 2018/12/20 00:00 [received] PHST- 2019/01/28 00:00 [revised] PHST- 2019/01/29 00:00 [accepted] PHST- 2019/02/06 06:00 [entrez] PHST- 2019/02/06 06:00 [pubmed] PHST- 2019/05/18 06:00 [medline] PHST- 2019/02/01 00:00 [pmc-release] AID - ijms20030625 [pii] AID - ijms-20-00625 [pii] AID - 10.3390/ijms20030625 [doi] PST - epublish SO - Int J Mol Sci. 2019 Feb 1;20(3):625. doi: 10.3390/ijms20030625.