ArticlePloS one2013
A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1β production by human first trimester trophoblast.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 104 citations in OpenAlex.
- Combined Obstetric and Thrombotic Complications Are Associated with Features Suggestive of an Immune-Enriched Phenotype Among Women with Thrombotic Antiphospholipid Syndrome (APS).Diagnostics (Basel, Switzerland) · 2026Article
- The Self-amplifying Inflammatory Cascade in Obstetric Antiphospholipid Syndrome: From Pathophysiology to Placenta-centric Immunotherapeutic Targets.Clinical reviews in allergy & immunology · 2026Review
- Immunometabolic Dysregulation in Preeclampsia: Emerging Roles of Inflammation, Insulin Resistance, Uric Acid, and the Gut Microbiome.Mediators of inflammation · 2026Review
- Extracellular vesicles in preeclampsia: drivers of vascular dysfunction and inflammation.American journal of physiology. Heart and circulatory physiology · 2025Review
- Placental Pathology in Obstetric Antiphospholipid Syndrome Beyond Thrombosis: A Case Report and Literature Review.Journal of clinical medicine · 2025Article
- Maternal Immune Activation: Implications for Congenital Heart Defects.Clinical reviews in allergy & immunology · 2025Review
- Understanding a Potential Role for the NLRP3 Inflammasome in Placenta-Mediated Pregnancy Complications.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Review
- Gaps in maternal-fetal interface rejection response: chronic histiocytic intervillositis.Frontiers in immunology · 2025Review
- NLRP3 Inflammasome in the Pathogenesis of Miscarriages.International journal of molecular sciences · 2024Article
- Molecular Determinants of Uterine Receptivity: Comparison of Successful Implantation, Recurrent Miscarriage, and Recurrent Implantation Failure.International journal of molecular sciences · 2023Review
- Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis.Journal of nanobiotechnology · 2023Article
- The pathogenesis of obstetric APS: a 2023 update.Clinical immunology (Orlando, Fla.) · 2023Review
- Trophoblast Cell Function in the Antiphospholipid Syndrome.Biomedicines · 2023Review
- From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children.International journal of molecular sciences · 2023Review
- Serum urea acid and urea nitrogen levels are risk factors for maternal and fetal outcomes of pregnancy: a retrospective cohort study.Reproductive health · 2022Article
- Mechanisms of immune regulation by the placenta: Role of type I interferon and interferon-stimulated genes signaling during pregnancy.Immunological reviews · 2022Review
- Antiphospholipid Antibodies Increase Endometrial Stromal Cell Decidualization, Senescence, and Inflammation via Toll-like Receptor 4, Reactive Oxygen Species, and p38 MAPK Signaling.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Anti‑βInternational journal of molecular medicine · 2022Article
- Human fetal membrane IL-1β production in response to bacterial components is mediated by uric-acid induced NLRP3 inflammasome activation.Journal of reproductive immunology · 2022Article
- Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Women with antiphospholipid syndrome (APS) are at risk of recurrent pregnancy loss and obstetrical disorders, such as preeclampsia and intrauterine growth restriction (IUGR). Antiphospholipid antibodies (aPL) directly target the placenta by binding beta2-glycoprotein I (β2GPI) expressed on the trophoblast. We recently demonstrated in human first trimester trophoblast cells that anti-β2GPI antibodies (Abs) induce the secretion of IL-1β in a Toll-like receptor 4 (TLR4)-dependent manner. IL-1β secretion requires processing of pro-IL-1β and this is mediated by the inflammasome, a complex of Nalp3, apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1. The objective of this study was to determine if aPL induce IL-1β production in trophoblast via the inflammasome. Using a human first trimester trophoblast cell line, we demonstrated that a mouse anti-β2GPI mAb and human polyclonal aPL-IgG induce IL-1β processing and secretion, which was partially blocked upon caspase-1 inhibition. Nalp3 and ASC knockdown also attenuated anti-β2GPI Ab-induced IL-1β secretion. Furthermore, aPL stimulated the production of uric acid in a TLR4-dependent manner; and inhibition of uric acid prevented aPL-induced IL-1β production by the trophoblast. These findings demonstrate that aPL, via TLR4 activation, induce a uric acid response in human trophoblast, which in turn activates the Nalp3/ASC inflammasome leading to IL-1β processing and secretion. This novel mechanism may account for the inflammation at the maternal-fetal interface, which causes placental dysfunction and increases the risk of adverse pregnancy outcome in patients with APS.
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Registered trials
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.