Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: The incidence of antibody-mediated kidney graft rejection continues to increase. We previously reported that dysregulated donor-specific antibody (DSA) responses were induced in B6.CCR5-/- mice transplanted with complete MHC mismatched A/J kidney allografts and that NK cells play a critical role in acute injury and graft failure. This acute antibody-mediated rejection is accompanied by intense macrophage infiltration into the allograft. The current study tested the role of recipient-derived myeloperoxidase (MPO) production on kidney allograft survival and on the production of DSA.B6.CCR5-/- and B6.CCR5-/-MPO-/- mice were transplanted with complete MHC mismatched A/J kidney grafts.
*Methods: B6.CCR5-/- and B6.CCR5-/-MPO-/- mice were transplanted with complete MHC mismatched A/J kidney grafts.
*Results: DSA titers in B6.CCR5-/-MPO-/- recipients were 4-5 fold lower than those induced in the B6.CCR5-/- recipients. Consistent with the pathogenic role of antibody in rejection of the kidney allografts, grafts were rejected between days 18 and 25 post-transplant in B6.CCR5-/- recipients but not until days 46-54 in B6.CCR5-/-MPO-/- recipients. There was also a 60% decrease in the number of donor-reactive T cells producing IFN-g in the spleens of the B6.CCR5-/-MPO-/- vs. B6.CCR5-/- recipients when assessed on day 7 post-transplant. When examined on day 14 post-transplant, kidney allografts from B6.CCR5-/- recipients were infiltrated with both NK1.1high and NK1.1low NK cells in an approximately 1:2 ratio, respectively, and the ratio of these NK cell populations was reversed in kidney allografts in B6.CCR5-/-MPO-/- recipients. Despite the extended survival, qPCR analyses indicated slight increases in mRNA encoding TNFa, IL-6 an FasL in kidney allografts on day 14 post-transplant in B6.CCR5-/-MPO-/- vs. B6.CCR5-/- recipients as well as the pro-fibrogenic factors connective tissue growth factor and P-selectin on day 50 post6-transplant.
*Conclusions: Overall, the results suggest that expression of MPO regulates the magnitude of the donor-specific antibody and T cell response in kidney transplant recipients and that the decreased DSA titers attenuate acute antibody graft rejection and may induce the indolent development of interstitial fibrosis and glomerular injury that will eventually lead to graft dysfunction and failure at later times.
To cite this abstract in AMA style:Miyairi S, Dvorina N, Valujuskikh A, 3rd WMBaldwin, Fairchild RL. Kidney Allograft Recipient Absence of Myeloperoxidase Decreases Donor-Specific Antibody Titers and Attenuates Antibody-Mediated Allograft Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/kidney-allograft-recipient-absence-of-myeloperoxidase-decreases-donor-specific-antibody-titers-and-attenuates-antibody-mediated-allograft-rejection/. Accessed March 9, 2021.
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