ArticleTransplantation2017
Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy.
Article in Transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Unraveling the Roles of Macrophages in Vascularized Composite Allotransplantation.Biomedicines · 2025Review
- Transcriptome profiling of immune rejection mechanisms in a porcine vascularized composite allotransplantation model.Frontiers in immunology · 2024Article
- 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
- Characterization of Novel P-Selectin Targeted Complement Inhibitors in Murine Models of Hindlimb Injury and Transplantation.Frontiers in immunology · 2021Article
- Article
- Efficacy of single-agent immunosuppressive regimens in a murine model of vascularized composite allotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2020Article
- Recent advances into the role of pattern recognition receptors in transplantation.Cellular immunology · 2020Review
- Vascular Signaling in Allogenic Solid Organ Transplantation - The Role of Endothelial Cells.Frontiers in physiology · 2020Review
- The complex functioning of the complement system in xenotransplantation.Xenotransplantation · 2019Review
- Emphysema-associated Autoreactive Antibodies Exacerbate Post-Lung Transplant Ischemia-Reperfusion Injury.American journal of respiratory cell and molecular biology · 2019Article
- Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Tissue-targeted complement therapeutics.Molecular immunology · 2018Review
- Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study.Bioscience reports · 2018Article
- Barriers and Advances in Kidney Preservation.BioMed research international · 2018Review
- Inhibition of Complement: Tackling of Both Innate and Adaptive Immune Responses to Dampen Rejection.Transplantation · 2017Article
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Authors and funding
6 authors at 2 institutions in 4 countries.
Funding
Abstract
backgroundRecipients of vascularized composite allografts require aggressive and lifelong immunosuppression, and because the surgery is usually performed in nonlife-threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy.
methodsVascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry). Allografts were analyzed for acute inflammation and injury, subacute T cell response, and survival in the absence and presence of cyclosporine A (CsA) therapy.
resultsAllografts in C3-deficient or CR2-Crry-treated recipients were protected from skin and muscle ischemia-reperfusion injury (IRI). C3aR/C5aR-deficient recipients were more modestly protected. IgM and C3d colocalized within allografts from wild type and C3aR/C5aR-deficient recipients indicating IgM-mediated complement activation, and C3d deposition was almost absent in allografts from C3-deficient and CR2-Crry-treated recipients. Inflammatory cell infiltration and P-selectin expression was also significantly reduced in C3-deficient and CR2-Crry-treated recipients. Acute treatment with CR2-Crry or with 3 mg/kg per day CsA modestly, but significantly increased median allograft survival from 5.8 to 7.4 and 7.2 days, respectively. However, combined acute CR2-Crry treatment and CsA therapy increased mean graft survival to 17.2 days. Protection was associated with significantly reduced T cell infiltration of allografts and Tc1 cells in recipient spleens.
conclusionsComplement-mediated IRI augments graft allogenicity, and appropriate complement inhibition ameliorates IRI, decreases alloimmune priming and allows more immune-sparing CsA dosing.
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