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. 2013 Apr;13(4):861-874.
doi: 10.1111/ajt.12168. Epub 2013 Feb 22.

Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury

H Cardinal  1 , M Dieudé  1 , N Brassard  1 , S Qi  1 , N Patey  2 , M Soulez  1 , D Beillevaire  1 , F Echeverry  3 , C Daniel  3 , Y Durocher  4 , F Madore  5 , M J Hébert  1
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Free article

Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury

H Cardinal et al. Am J Transplant. 2013 Apr.
Free article

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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Comment in

  • Antibodies beyond HLA.
    Nickerson PW, Rush DN. Nickerson PW, et al. Am J Transplant. 2013 Apr;13(4):831-832. doi: 10.1111/ajt.12160. Epub 2013 Feb 13. Am J Transplant. 2013. PMID: 23406413 No abstract available.

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