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Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury.

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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https://hal-riip.archives-ouvertes.fr/pasteur-01130364
Contributor : Michel Courcelles Connect in order to contact the contributor
Submitted on : Wednesday, March 11, 2015 - 4:02:05 PM
Last modification on : Monday, July 20, 2020 - 12:33:14 PM

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H Cardinal, M Dieudé, N Brassard, S Qi, N Patey, et al.. Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury.. American Journal of Transplantation, Wiley, 2013, 13 (4), pp.861-74. ⟨10.1111/ajt.12168⟩. ⟨pasteur-01130364⟩

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