| DOI | Resolve DOI: https://doi.org/10.1111/ajt.12168 |
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| Author | Search for: Cardinal, H.; Search for: Dieudé, M.; Search for: Brassard, N.; Search for: Qi, S.; Search for: Patey, N.; Search for: Soulez, M.; Search for: Beillevaire, D.; Search for: Echeverry, F.; Search for: Daniel, C.; Search for: Durocher, Y.1; Search for: Madore, F.; Search for: Hébert, M. J. |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | 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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| Abstract | 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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| Publication date | 2013-02-22 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21270524 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | b4f72186-6ae3-4377-9fd9-c8f6465dddd7 |
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| Record created | 2014-02-17 |
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| Record modified | 2020-04-22 |
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