Preeclampsia: a view through the danger model
Open accessAbstract
Classical thinking suggests that the immune system undergoes activation on the basis of discrimination between 'self' and 'non-self'. Accordingly, the fetus activates the mother's immune system because the fetus is in part 'non-self'. Thus, successful pregnancy depends on constraint of maternal immunity. Preeclampsia is an outcome of lost constraint. Instead, the danger model suggests that normal pregnancy, regardless of the expression of 'non-self' antigens, does not activate the maternal immune system unless that pregnancy expresses danger signals. Thus, preeclampsia stems from stress or abnormal cell death in pregnancy-related tissues. This compels expression of specific danger signals and potential activation of anti-fetal immunity, which secondarily feeds the syndrome. Study of preeclampsia from this perspective may bring forth novel mechanisms and indicators of vascular and metabolic dysfunction during pregnancy.
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An influx of mitochondrial DNA into the maternal circulation may act as a danger signal/alarmin responsible for the sterile intravascular inflammatory processes of preeclampsia.
“suggesting that an influx of mitochondrial DNA into the maternal circulation may act as a danger signal/alarmin responsible for the sterile (absence of infection) intravascular inflammatory processes of this condition(202, 203)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [202]
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“Poor placentation, oxidative stress, endothelial cell dysfunction and altered glucose metabolism among others generate Damage-Associated Molecular Patterns (DAMPs) including Heat Shock Proteins (HSPs), TNF-α, fetal DNA, hyaluronan, oxidised low-density lipoprotein (LDL) and long pentraxin-3 [36].”
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Chaouat, G. (2017) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2017.06.002 · Cited by 3 · see citing works
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“Whilst NK cells are important for placentation, an exaggerated presence of NK cells may lead to complications during pregnancy [29].”
BackgroundPrediction of Maternal and Fetal Syndrome of Preeclampsia
Sharma, N. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.78845 · Cited by 3 · see citing works
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IMMUNE MECHANISM OF PREECLAMPSIA
Wantania, J. J. E. (2015) · Jurnal Biomedik JBM · doi:10.35790/jbm.7.2.2015.9323 · Cited by 1 · see citing works
“If the balance between cells is disrupted where peroxidase and oxidants become more dominant, then there will be a condition called oxidative stress.(5,9)”
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Schwangerschaft und maternales Immunsystem
Scholz, C., Rogenhofer, N. N., Jeschke, U., Thaler, C., & Tóth, B. (2009) · Der Gynäkologe · doi:10.1007/s00129-008-2228-3 · Cited by 1 · see citing works
Shaaban, Y. H., Aletebi, F. A., Helal, M. M., & Saber, W. (2012) · Evidence Based Women s Health Journal · doi:10.1097/01.ebx.0000415828.84622.0c
Preeclampsia and damage — associated molecular patterns
Shcherbakov, V. I., Михайлович, П. И., & Владимировна, Ш. А. (2021) · Russian Bulletin of Obstetrician-Gynecologist · doi:10.17116/rosakush20212104120
Akevwighome, S., Chinko, B. C., Ojeka, S. O., Green, K., & Dapper, D. V. (2024) · Science Frontiers · doi:10.11648/j.sf.20240502.11
Zu, C., Li, M., Ren, S., Chen, N., Ye, L., & Guo, R. (2025) · Food and Chemical Toxicology · doi:10.1016/j.fct.2025.115912
T cells, placentation, gestational length and an evolutionary perspective relevant to preterm birth
Bonney, E. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-21564-3.00019-2
- Authors
- Bonney, E. A.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Bonney, Elizabeth A.
- ORCID
- Bonney, Elizabeth A.
- Venue
- Journal of Reproductive Immunology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 76
- Issue
- 1-2
- Pages
- 68-74
- ISSN
- 0165-0378 (ISSN-L)
- PMC
- PMC2246056
- OpenAlex
- W1989862594
- Cited by
- 53
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Reproductive Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (R01 043185, R01 047224)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD043185)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy-related medical research
- Keywords
- preeclampsia, danger model, maternal immune activation, pregnancy, damage-associated molecular patterns, maternal-fetal immune tolerance, vascular dysfunction, metabolic dysfunction, self/non-self discrimination
- MeSH terms
- Female, Fetal Death, Fetus, Humans, Immune Tolerance, Maternal-Fetal Exchange, Models, Biological, Placenta, Pre-Eclampsia, Pregnancy, HELLP Syndrome
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