ArticleThe Journal of clinical investigation2024
IgG hexamers initiate complement-dependent acute lung injury.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Neutrophil NADPH oxidase breaks the inflammatory IL-1β/IL-17A circuit to enhance pathogen clearance during respiratory virus infections.Nature communications · 2026Article
- Fcγ-receptor-activation by circulating immune complexes in systemic autoimmune diseases and its reduction by CD19-CAR T cell therapy.Rheumatology (Oxford, England) · 2026Article
- Immobilized IgG-containing immune complexes require platelets to recruit neutrophils during inflammation.The Journal of clinical investigation · 2026Article
- Pulmonary Vascular Endothelial Cells in Lung Diseases: Mechanisms, Therapeutic Strategies, and Future Directions.Cell proliferation · 2026Review
- Article
- Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI.Blood · 2025Article
- Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.The Journal of experimental medicine · 2025Article
- Primary graft dysfunction after Lung transplantation: unveiling the role of innate immunity.Clinical and experimental immunology · 2025Article
- Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.bioRxiv : the preprint server for biology · 2024Article
- The importance of disrupting complement activation in acute lung injury.The Journal of clinical investigation · 2024Article
- Reply: The importance of disrupting complement activation in acute lung injury.The Journal of clinical investigation · 2024Article
- Hexamerization: explaining the original sin of IgG-mediated complement activation in acute lung injury.The Journal of clinical investigation · 2024Article
- Loss of neutrophil Shp1 produces hemorrhagic and lethal acute lung injury.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, in reactions to transfusions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful antibodies often activate the complement cascade. A model for how IgG antibodies trigger complement activation involves interactions between IgG Fc domains driving the assembly of IgG hexamer structures that activate C1 complexes. The importance of IgG hexamers in initiating injury responses was not clear, so we tested their relevance in a mouse model of alloantibody- and complement-mediated acute lung injury. We used 3 approaches to block alloantibody hexamerization (antibody carbamylation, the K439E Fc mutation, or treatment with domain B from staphylococcal protein A), all of which reduced acute lung injury. Conversely, Fc mutations promoting spontaneous hexamerization made a harmful alloantibody into a more potent inducer of acute lung injury and rendered an innocuous alloantibody pathogenic. Treatment with a recombinant Fc hexamer "decoy" therapeutic protected mice from lung injury, including in a model with transgenic human FCGR2A expression that exacerbated pathology. These results indicate an in vivo role of IgG hexamerization in initiating acute lung injury and the potential for therapeutics that inhibit or mimic hexamerization to treat antibody-mediated diseases.
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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.