ArticleBlood2015
Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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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.
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.
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Who cites it
54 citing papers in PubMed, 99 citations in OpenAlex.
- Trial
- Three cryo-EM structures of complement C3d-bound αScience advances · 2026Article
- PNH extravascular hemolysis: exploring clinical significance.Blood advances · 2026Article
- Design of miniprotein inhibitors targeting complement C9 to block membrane attack complex assembly.Nature communications · 2026Article
- Article
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Determining Ligand Binding and Specificity Within the βBiomolecules · 2025Article
- Successful treatment of transplant-associated thrombotic microangiopathy with iptacopan: a non-adult case study.Frontiers in immunology · 2025Article
- [Paroxysmal nocturnal hemoglobinuria during pregnancy: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Review
- Navigating the Complement Pathway to Optimize PNH Treatment with Pegcetacoplan and Other Currently Approved Complement Inhibitors.International journal of molecular sciences · 2024Review
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- SAR443809: a selective inhibitor of the complement alternative pathway, targeting complement factor Bb.Blood advances · 2023Article
- Complement Drives Chronic Inflammation and Progressive Hydrocephalus in Murine Neonatal Germinal Matrix Hemorrhage.International journal of molecular sciences · 2023Article
- Protein therapeutics and their lessons: Expect the unexpected when inhibiting the multi-protein cascade of the complement system.Immunological reviews · 2023Review
- The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.Immunological reviews · 2023Review
- Effects of β2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis.Biomolecules · 2022Review
- Novel Insights into Factor D Inhibition.International journal of molecular sciences · 2022Review
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
- The Rational Use of Complement Inhibitors in Kidney Diseases.Kidney international reports · 2022Review
- How we('ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future.British journal of haematology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The clinical management of paroxysmal nocturnal hemoglobinuria (PNH), a rare but life-threatening hematologic disease, has fundamentally improved with the introduction of a therapeutic that prevents complement-mediated intravascular hemolysis. However, a considerable fraction of PNH patients show insufficient treatment response and remain transfusion dependent. Because the current treatment only prevents C5-induced lysis but not upstream C3 activation, it has been speculated that ongoing opsonization with C3 fragments leads to recognition and phagocytosis of PNH erythrocytes by immune cells. Here, for the first time, we provide experimental evidence for such extravascular hemolysis and demonstrate that PNH erythrocytes from anti-C5-treated patients are phagocytosed by activated monocytes in vitro. Importantly, we show that this uptake can be mediated by the end-stage opsonin C3dg, which is not traditionally considered a phagocytic marker, via interaction with complement receptor 3 (CR3). Interaction studies confirmed that C3dg itself can act as a ligand for the binding domain of CR3. The degree of C3dg-mediated erythrophagocytosis in samples from different PNH patients correlated well with the individual level of C3dg opsonization. This finding may guide future treatment options for PNH but also has potential implications for the description and management of other complement-mediated diseases.
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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.