ArticleCirculation2015
Targeting pathogenic postischemic self-recognition by natural IgM to protect against posttransplantation cardiac reperfusion injury.
Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Best practices of heart transplantation in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice.World journal of hepatology · 2024Article
- The immunology of B-1 cells: from development to aging.Immunity & ageing : I & A · 2024Review
- A single-chain antibody construct with specificity of a natural IgM antibody reduces hepatic ischemia reperfusion injury in mice.Journal of cellular and molecular medicine · 2024Article
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Highly pathogenic natural monoclonal antibody B4-IgM recognizes a post-translational modification comprised of acetylated N-terminal methionine followed by aspartic or glutamic acid.Molecular immunology · 2023Article
- TNFRSF13B in B cell responses to organ transplantation.Human immunology · 2023Article
- Higher levels of allograft injury in black patients early after heart transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Article
- Article
- Increasing the efficacy and safety of a human complement inhibitor for treating post-transplant cardiac ischemia reperfusion injury by targeting to a graft-specific neoepitope.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2021Article
- Natural immunoglobulin M-based delivery of a complement alternative pathway inhibitor in mouse models of retinal degeneration.Experimental eye research · 2021Article
- A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Set Up for Failure: Pre-Existing Autoantibodies in Lung Transplant.Frontiers in immunology · 2021Review
- Characterization of Novel P-Selectin Targeted Complement Inhibitors in Murine Models of Hindlimb Injury and Transplantation.Frontiers in immunology · 2021Article
- Complement-Dependent Synaptic Uptake and Cognitive Decline after Stroke and Reperfusion Therapy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- C2 IgM Natural Antibody Enhances Inflammation and Its Use in the Recombinant Single Chain Antibody-Fused Complement Inhibitor C2-Crry to Target Therapeutics to Joints Attenuates Arthritis in Mice.Frontiers in immunology · 2020Article
- The five dimensions of B cell tolerance.Immunological reviews · 2019Review
- Emphysema-associated Autoreactive Antibodies Exacerbate Post-Lung Transplant Ischemia-Reperfusion Injury.American journal of respiratory cell and molecular biology · 2019Article
- Role of Complement Activation in Allograft Inflammation.Current transplantation reports · 2019Article
- Tissue-targeted complement therapeutics.Molecular immunology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundNatural IgM antibodies represent a class of innate pattern recognition receptors that recognize danger-associated molecular patterns expressed on stressed or dying cells. They play important roles in tissue homeostasis by disposing of prenecrotic cells and suppressing inflammation. However, ischemic insult leads to a pathogenic level of IgM binding and complement activation, resulting in inflammation and injury. We investigate the role of self-reactive IgM in the unique setting of transplantation where the donor organ undergoes both cold and warm ischemia and global ischemic insult. METHODS AND
resultsBy transplanting hearts from wild-type donor mice into antibody-deficient mice reconstituted with specific self-reactive IgM monoclonal antibodies, we identified neoepitopes expressed after transplantation and demonstrated a key role for IgM recognition of these epitopes in graft injury. With this information, we developed and characterized a therapeutic strategy that exploited the postischemia recognition system of natural antibodies. On the basis of neoepitope identification, we constructed an anti-annexin IV single-chain antibody (scFv) and an scFv linked to Crry, an inhibitor of C3 activation (scFv-Crry). In an allograft transplantation model in which recipients contain a full natural antibody repertoire, both constructs blocked graft IgM binding and complement activation and significantly reduced graft inflammation and injury. Furthermore, scFv-Crry specifically targeted to the transplanted heart and, unlike complement deficiency, did not affect immunity to infection, an important consideration for immunosuppressed transplant recipients.
conclusionsWe identified pathophysiologically important epitopes expressed within the heart after transplantation and described a novel translatable strategy for targeted complement inhibition that has several advantages over currently available approaches.
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