Date: Sunday, June 2, 2019
Session Name: Concurrent Session: B-cell / Antibody /Autoimmunity
Session Time: 4:30pm-6:00pm
Presentation Time: 5:42pm-5:54pm
Location: Room 310
*Purpose: Prolonged cold ischemia storage (CIS) of donor transplants is a major risk factor for acute and chronic graft tissue injury.The goal of this study was to test how increased CIS time influences alloimmunity using a mouse model of renal transplantation.
*Methods: B6 (H-2b) mice received BALB/c (H-2d) renal allografts subjected to 0.5 h or 6 h CIS in University of Wisconsin solution (0.5 h CIS and 6 h CIS groups).
*Results: At d.14 posttransplant, recipients from 6 h CIS group had increased titers of donor-MHC class II but not class I reactive IgG alloantibodies, higher frequencies of donor-reactive IFNγ secreting T cells and significantly higher proportion of glomeruli infiltrated with macrophages compared to 0.5 h CIS controls. By d.60 posttransplant, 6 h CIS but not 0.5h CIS allografts developed extensive glomerular injury including thickened capillary loops, segmental or global sclerosis and thrombotic microangiopathy with red cell congestion, intracapillary fibrin thrombi, and mesangiolysis. B cell depletion with anti-mouse CD20 mAb inhibited DSA generation, intragraft C4d deposition and macrophage glomerular infiltration on d.14 posttransplant. These data strongly suggest that the initial glomerular injury following prolonged CIS is alloantibody-mediated. Treatment of 6 h CIS recipients with sphingosine-1-phosphate receptor 1 agonist (FTY720) reduced number of circulating T and B lymphocytes and inhibited the development of anti-MHC class II reactive DSA. Despite the presence of anti MHC class I DSA recipients treated with FTY720 had minimal vascular C4d deposition and reduced macrophage infiltration in glomeruli on day +14. Adoptive transfer of anti-donor MHC class II containing sera or monoclonal antibody into FTY720 treated recipients partially restored macrophage glomerular infiltrate
*Conclusions: These results indicate that posttransplant inflammation not only facilitates DSA development but also spreads the specificity of DSA from donor class I to class II and may thus influence renal allograft pathology. This is first demonstartion for the pathogenic role of MHC class II reactive DSA in transplant glomerulopathy.
To cite this abstract in AMA style:Gorbacheva V, Fan R, Beavers A, Fairchild R, Baldwin W, Valujskikh A. Anti-Donor M H C Class I I Alloantibody Induce Glomerular Injury in Mouse Renal Allografts Subjected to Prolonged Cold Ischemia [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/anti-donor-m-h-c-class-i-i-alloantibody-induce-glomerular-injury-in-mouse-renal-allografts-subjected-to-prolonged-cold-ischemia/. Accessed December 5, 2019.
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