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Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury

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Cardinal, Héloïse, Dieudé, Mélanie, Brassard, Nathalie, Qi, Shijie, Patey, Nathalie, Soulez, Mathilde, Beillevaire, Deborah, Echeverry-Alzate, Fernando, Daniel, Claude, Durocher, Yves, Madore, François et Hébert, Marie-Josée (2013). Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury American Journal of Transplantation , vol. 13 , nº 4. p. 861-874. DOI: 10.1111/ajt.12168.

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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.

Type de document: Article
Mots-clés libres: acute rejection ; antibodies ; apoptosis ; kidney transplantation
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 26 mai 2017 15:19
Dernière modification: 16 févr. 2021 14:09
URI: https://espace.inrs.ca/id/eprint/2872

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