| DOI | Trouver le DOI : https://doi.org/10.1111/ajt.12168 |
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| Auteur | Rechercher : Cardinal, H.; Rechercher : Dieudé, M.; Rechercher : Brassard, N.; Rechercher : Qi, S.; Rechercher : Patey, N.; Rechercher : Soulez, M.; Rechercher : Beillevaire, D.; Rechercher : Echeverry, F.; Rechercher : Daniel, C.; Rechercher : Durocher, Y.1; Rechercher : Madore, F.; Rechercher : Hébert, M. J. |
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| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Sujet | acute rejection; antibody; calcineurin inhibitor; CD4 antigen; immunoglobulin G; perlecan; animal experiment; antibody titer; apoptosis; blood vessel injury; endothelium cell; graft recipient; graft survival; immune mediated injury; immunoglobulin A nephropathy; kidney allograft rejection; kidney transplantation; neointima; protein function |
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| Résumé | Acute vascular rejection (AVR) is characterized by immune-mediated vascular injury and heightened endothelial cell (EC) apoptosis. We reported previously that apoptotic ECs release a bioactive C-terminal fragment of perlecan referred to as LG3. Here, we tested the possibility that LG3 behaves as a neoantigen, fuelling the production of anti-LG3 antibodies of potential importance in regulating allograft vascular injury. We performed a case-control study in which we compared anti-LG3 IgG titers in kidney transplant recipients with AVR (n = 15) versus those with acute tubulo-interstitial rejection (ATIR) (n = 15) or stable graft function (n = 30). Patients who experienced AVR had elevated anti-LG3 titers pre and posttransplantation compared to subjects with ATIR or stable graft function (p < 0.05 for both mediators). Elevated pretransplant anti-LG3 titers (OR: 4.62, 95% CI: 1.08-19.72) and pretransplant donor-specific antibodies (DSA) (OR 4.79, 95% CI: 1.03-22.19) were both independently associated with AVR. To address the functional role of anti-LG3 antibodies in AVR, we turned to passive transfer of anti-LG3 antibodies in an animal model of vascular rejection based on orthotopic aortic transplantation between fully MHC-mismatched mice. Neointima formation, C4d deposition and allograft inflammation were significantly increased in recipients of an ischemic aortic allograft passively transferred with anti-LG3 antibodies. Collectively, these data identify anti-LG3 antibodies as novel accelerators of immune-mediated vascular injury and obliterative remodeling. |
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| Date de publication | 2013-02-22 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 21270524 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | b4f72186-6ae3-4377-9fd9-c8f6465dddd7 |
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| Enregistrement créé | 2014-02-17 |
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| Enregistrement modifié | 2020-04-22 |
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