Satu Wedenoja, Masahito Yoshihara, Hindrek Teder, Hannu Sariola, Mika Gissler, Shintaro Katayama, Juho Wedenoja, Inka M. Häkkinen, Sini Ezer, Nina Linder, Johan Lundin, Tiina Skoog, Ellika Sahlin, Erik Iwarsson, Karin Pettersson, Eero Kajantie, Mikael Mokkonen, Seppo Heinonen, Hannele Laivuori, Kaarel Krjutškov, Juha Kere, Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia, EBioMedicine, Volume 59, 2020, 102872, ISSN 2352-3964, https://doi.org/10.1016/j.ebiom.2020.102872
Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
|Author:||Wedenoja, Satu1,2; Yoshihara, Masahito3; Teder, Hindrek4,5;|
1Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
2Stem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland
3Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden
4Competence Centre of Health Technologies, 50411 Tartu, Estonia
5Institute of Biomedicine and Translational Medicine, University of Tartu, 50090 Tartu, Estonia
6University of Helsinki and HUSLAB Pediatric Pathology, 00290 Helsinki, Finland
7Information Services Department, Finnish Institute for Health and Welfare, 00300 Helsinki, Finland
8Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 17177 Stockholm, Sweden
9Research Centre for Child Psychiatry, University of Turku, 20500 Turku, Finland
10Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
11Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, 00290 Helsinki, Finland
12Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, 75105 Uppsala, Sweden
13Department of Public Health Sciences, Karolinska Institutet, 17177 Stockholm, Sweden
14Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, 17176 Stockholm, Sweden
15Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, and Department of Obstetrics, Karolinska University Hospital, 17176 Stockholm, Sweden
16Public Health Promotion Unit, Finnish Institute for Health and Welfare, 00300 Helsinki and 90220 Oulu, Finland
17PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, 90570 Oulu, Finland
18Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
19Children's Hospital, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland
20Department of Biology, Kwantlen Polytechnic University, Surrey, BC V3W 2M8, Canada
21Department of Biological Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada
22Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
23Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, 33520 Tampere, Finland
|Online Access:||PDF Full Text (PDF, 1.9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020120399318
|Publish Date:|| 2020-12-03
Background: Fetal 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.
Methods: We 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.
Findings: We 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.
Interpretation: These 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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3123 Gynaecology and paediatrics
Finnish 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.
© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/).