Evidence map›Paper›PMID 32680723›Full record

ArticleEBioMedicine2020

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

Satu Wedenoja, Masahito Yoshihara, Hindrek Teder, Hannu Sariola, Mika Gissler, Shintaro Katayama, Juho Wedenoja, Inka M Häkkinen, Sini Ezer, Nina Linder and 11 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 48 citations in OpenAlex.

  1. Observational
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  3. HLA-G, IL-6 and TGF-β in Seminal Plasma as Potential Biomarkers of ART Outcome.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 5 countries.

Satu WedenojaObstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Stem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland. Electronic address: satu.wedenoja@helsinki.fi.
Masahito YoshiharaDepartment of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.
Hindrek TederCompetence Centre of Health Technologies, 50411 Tartu, Estonia; Institute of Biomedicine and Translational Medicine, University of Tartu, 50090 Tartu, Estonia.
Hannu SariolaUniversity of Helsinki and HUSLAB Pediatric Pathology, 00290 Helsinki, Finland.
Mika GisslerInformation Services Department, Finnish Institute for Health and Welfare, 00300 Helsinki, Finland; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 17177 Stockholm, Sweden; Research Centre for Child Psychiatry, University of Turku, 20500 Turku, Finland.
Shintaro KatayamaStem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.
Juho WedenojaDepartment of Ophthalmology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland.
Inka M HäkkinenStem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland.
Sini EzerStem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland.
Nina LinderInstitute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, 00290 Helsinki, Finland; Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, 75105 Uppsala, Sweden.
Johan LundinInstitute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, 00290 Helsinki, Finland; Department of Public Health Sciences, Karolinska Institutet, 17177 Stockholm, Sweden.
Tiina SkoogDepartment of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.
Ellika SahlinDepartment of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, 17176 Stockholm, Sweden.
Erik IwarssonDepartment of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, 17176 Stockholm, Sweden.
Karin PetterssonDepartment of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, and Department of Obstetrics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Eero KajantiePublic Health Promotion Unit, Finnish Institute for Health and Welfare, 00300 Helsinki and 90220 Oulu, Finland; PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, 90570 Oulu, Finland; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Children's Hospital, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland.
Mikael MokkonenDepartment of Biology, Kwantlen Polytechnic University, Surrey, BC V3W 2M8, Canada; Department of Biological Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Seppo HeinonenObstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland.
Hannele LaivuoriInstitute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, 00290 Helsinki, Finland; Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, 33520 Tampere, Finland.
Kaarel KrjutškovStem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden; Competence Centre of Health Technologies, 50411 Tartu, Estonia.
Juha KereStem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden. Electronic address: juha.kere@ki.se.
University of Helsinki · FIKarolinska University Hospital · SEKarolinska Institutet · SECompetence Centre on Health Technologies (Estonia) · EESimon Fraser University · CAUniversity of Turku · FIUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFetal 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.

methodsWe 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.

findingsWe 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.

interpretationThese 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.

fundingFinnish Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Karolinska Institutet Research Foundation, Scandinavia-Japan Sasakawa Foundation, Japan Eye Bank Association, Astellas Foundation for Research on Metabolic Disorders, Japan Society for the Promotion of Science, Knut and Alice Wallenberg Foundation, Swedish Research Council, Medical Society Liv och Hälsa, Sigrid Jusélius Foundation, Helsinki University Hospital and University of Helsinki, Jane and Aatos Erkko Foundation, Academy of Finland, Finska Läkaresällskapet, Novo Nordisk Foundation, Finnish Foundation for Pediatric Research, and Emil Aaltonen Foundation.

Indexed as

Immune Tolerance3' Untranslated RegionsAllelesDisease SusceptibilityFemaleHLA-G AntigensHomozygoteHumansInterferonsMaleMaternal-Fetal ExchangeOdds RatioPlacentaPre-EclampsiaPregnancyPregnancy Outcome3' Untranslated RegionsHLA-G AntigensInterferonsBalancing selectionHLA-GInterferon alphaPreeclampsiaSex ratioStillbirth

Identifiers

PMID32680723
PMCPMC7502669
OpenAlexW3042903999

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.