Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
[Background] Sensitization before transplantation and de novo alloantibodies affect a significant number of patients awaiting kidney transplantation. The type of anti-HLA antibody varies with subgroups that express MHC class I alone, MHC class II alone or both. The mechanisms that direct MHC Class I or II sensitization are not well understood. Using a non-human primate model of sensitization, we have performed a series of experiments to investigate the mechanisms involved in donor specific sensitization. With this data we report that a unique combination of donor antigen combined with adjuvant therapy results in MHC class II specific sensitization.
[Methods] Thirteen fully mismatched rhesus macaques were sensitized via skin exchange (SKIN-group). Four comparable animals twice received equal amounts of donor peripheral blood mononuclear cells (PBMC-group) intravenously and intradermally, the latter after adsorption with aluminum hydroxide gel suspension as adjuvant. Immunologic responses were monitored by T- and B-cell flow crossmatches (FXM). FXM were considered positive when reaching MFI-ratio > 2 (two-fold MFI value compared to baseline). We correlated FXM results with the human FlowPRA bead assay in 1 animal of each group.
[Results] All SKIN-animals showed a positive T- and B-cell FXM at peak (mean MFI-ratios 9.2+/-7.1 and 6.5+/-3.2 respectively). PBMC-animals showed negative T-cell FXM at all time points (mean peak 1.49+/-0.3), but all had a strongly positive B-cell FXM (mean peak 9.19+/-4.9). The FlowPRA assay was positive for MHC class I and II in the SKIN-animal but isolated positive for class II in the PBMC-animal.
[Conclusion] These results suggest that MHC class II specific sensitization may be controlled by inflammatory signals during donor antigens sensitization. Although the mechanism of this phenomenon is unclear, these results support further investigation into the role of innate immunologic mechanisms during sensitization.
To cite this abstract in AMA style:Burghuber C, Kwun J, Gibby A, Iwakoshi N, Knechtle S. MHC-Class-II Specific Sensitization in a Non-Human Primate Model of Sensitzation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/mhc-class-ii-specific-sensitization-in-a-non-human-primate-model-of-sensitzation/. Accessed April 15, 2021.
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