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A novel mouse model of acute antibody-mediated transplant rejection shows simultaneous complement activating and anti-inflammatory effects of donor specific IgG antibodies

  • Author / Creator
    Chow, Aaron K.Y.
  • We developed a small animal model of pure antibody-mediated rejection (ABMR) by utilizing fully major histocompatibility complex (MHC) mismatched kidney allografts in mice. By examining resultant ABMR pathology, we show that terminal complement products C5a and C5b-9 are crucial in establishing antibody-mediated allograft microvascular and tubular injury, and the presence of proximal complement product C4d alone is not indicative of ABMR. We demonstrate allorecognition capabilities in NK cells to induce micro-inflammation and apoptosis in MHC mismatched transplants. By gene expression profiling, we found that binding of donor specific antibodies (DSA) into kidney allograft tissues induces a ‘self-protective’ anti-inflammatory response in kidney parenchyma. The data suggests that the anti-inflammatory response associated with DSA may be regulated via inhibitory Fc receptors for immunoglobulin G. In summary, we established a mouse model demonstrating pure acute ABMR of kidney allografts mimicking some aspects of human ABMR pathology in the absence of T cell-mediated rejection.

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3BX08
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Medical Sciences- Laboratory Medicine and Pathology
  • Supervisor / co-supervisor and their department(s)
    • Hugh, Judith (Laboratory Medicine and Pathology)
    • Sis, Banu (Laboratory Medicine and Pathology)
  • Examining committee members and their departments
    • Murray, Allan (Medicine)
    • Mengel, Michael (Laboratory Medicine and Pathology)