ArticleBlood advances2018
Complement C5 but not C3 is expendable for tissue factor activation by cofactor-independent antiphospholipid antibodies.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Tissue factor in COVID-19-associated coagulopathy.Thrombosis research · 2022Pooled it
- Workflow for Accurate Measurement of PDI Reductase Kinetics Using a Fluorescent Disulfide Substrate.microPublication biology · 2026Article
- The Role of Hydroxychloroquine in the Management of Rheumatic Disorders: A Comprehensive Review.Basic & clinical pharmacology & toxicology · 2025Review
- Hydroxychloroquine: A double‑edged sword (Review).Molecular medicine reports · 2025Review
- Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.Blood · 2024Article
- Molecular Linkage between Immune System Disorders and Atherosclerosis.Current issues in molecular biology · 2023Review
- The role of coagulome in the tumor immune microenvironment.Advanced drug delivery reviews · 2023Review
- A targeted activatable NIR-II nanoprobe for positive visualization of anastomotic thrombosis and sensitive identification of fresh fibrinolytic thrombus.Materials today. Bio · 2023Article
- Tissue factor in cancer-associated thromboembolism: possible mechanisms and clinical applications.British journal of cancer · 2022Review
- Emerging Therapies in Antiphospholipid Syndrome.Transfusion medicine reviews · 2022Review
- The complement system and autoimmune diseases.Chronic diseases and translational medicine · 2022Review
- Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019.British journal of pharmacology · 2022Article
- Risk of Thrombosis, Pregnancy Morbidity or Death in Antiphospholipid Syndrome.Frontiers in cardiovascular medicine · 2022Review
- The role of the complement system in kidney glomerular capillary thrombosis.Frontiers in immunology · 2022Review
- ERO1-PDI Redox Signaling in Health and Disease.Antioxidants & redox signaling · 2021Review
- Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19.Journal of thrombosis and haemostasis : JTH · 2021Article
- Monocyte activation and acquired autoimmune protein S deficiency promote disseminated intravascular coagulation in a patient with primary antiphospholipid syndrome.Research and practice in thrombosis and haemostasis · 2021Article
- Is complement the culprit behind COVID-19 vaccine-related adverse reactions?The Journal of clinical investigation · 2021Review
- Lipid presentation by the protein C receptor links coagulation with autoimmunity.Science (New York, N.Y.) · 2021Article
- Antiphospholipid syndrome: Complement activation, complement gene mutations, and therapeutic implications.Journal of thrombosis and haemostasis : JTH · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement and coagulation cascades interact at multiple levels in thrombosis and inflammatory diseases. In venous thrombosis, complement factor 3 (C3) is crucial for platelet and tissue factor (TF) procoagulant activation dependent on protein disulfide isomerase (PDI). Furthermore, C5 selectively contributes to the exposure of leukocyte procoagulant phosphatidylserine (PS), which is a prerequisite for rapid activation of monocyte TF and fibrin formation in thrombosis. Here, we show that monoclonal cofactor-independent antiphospholipid antibodies (aPLs) rapidly activate TF on myelomonocytic cells. TF activation is blocked by PDI inhibitor and an anti-TF antibody interfering with PDI binding to TF, and requires C3 but unexpectedly not C5. Other prothrombotic, complement-fixing antibodies, for example, antithymocyte globulin, typically induce TF activation dependent on C5b-7-mediated PS exposure on the outer membrane of monocytes. We show that aPLs directly induce procoagulant PS exposure independent of C5. Accordingly, mice deficient in C3, but not mice deficient in C5, are protected from in vivo thrombus formation induced by cofactor-independent aPLs. Only immunoglobulin G (IgG) fractions with cofactor-independent anticardiolipin reactivity from patients with antiphospholipid syndrome (APS) induce complement-independent monocyte PS exposure and PDI-dependent TF activation. Neither a human monoclonal aPL directed against β2-glycoprotein I (β2GPI) nor patient IgG with selective reactivity to β2GPI rapidly activated monocyte TF. These results indicate that inhibitors of PDI and TF, but not necessarily clinically available drugs targeting C5, have therapeutic benefit in preventing thrombosis associated with APS caused by pathogenic aPLs primarily reactive with lipid, independent of β2GPI.
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