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Abstract: FR-PO859

Variability in Outcome in Patients with DSAs Is Modulated by the Expression of HLA Antigens on the Allograft Endothelium

Session Information

  • Transplantation: Basic
    October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1801 Transplantation: Basic

Authors

  • Beland, Stephanie, University Health Center (CHU) of Quebec, Laval University, Quebec, Quebec, Canada
  • Bouchard-Boivin, François, University Health Center (CHU) of Quebec, Laval University, Quebec, Quebec, Canada
  • Desy, Olivier, University Health Center (CHU) of Quebec, Laval University, Quebec, Quebec, Canada
  • De Serres, Sacha A., University Health Center (CHU) of Quebec, Laval University, Quebec, Quebec, Canada
Background

The development of de novo donor-specific antibodies (DSAs) is associated with antibody-mediated rejection and allograft failure. However, some patients with DSAs escape graft rejection. We hypothesized that DSA-mediated injury is modulated by 1) the variability in expression of HLA-II antigen subtypes (DR, DP and DQ) on a within-patient basis and 2) the variability in HLA antigen expression on a between-patient basis.

Methods

We measured in vitro HLA-I and II (DR, DP and DQ subtypes) antigen expression on 2 glomerular endothelial cell lines and on blood outgrowth endothelial cells (BOEC) from patient's collected PBMCs (n=12). Endothelial cells were treated following a time-course of IFN-g for 10 days to induce HLA-II expression. HLA antigen expression was assessed by flow cytometry over time. Unstimulated cells were used as controls.

Results

Across all individuals, the maximal percentage and the standard deviation of HLA-positive cells varied substantially (97±3 vs. 96±3 vs. 89±9 vs. 44±37% for HLA-I vs. –DR vs. –DP, vs –DQ respectively, p<0.001) as well as the time of incubation to reach maximal expression (5±2 vs. 4±1 vs. 6±2 vs. 9±1days, p<0.001). Maximal MFI also varied between HLA subtypes (98±49 vs. 12±8 vs. 10±6 vs. 4±3x103, p<0.001) as well as the time to reach this maximum (4±1 vs. 6±2 vs. 8±2 vs. 10±1days, p<0.001). Repeated experiments on the same individuals showed little variation between experiments (mean SD 12±8 vs. 7±5 vs. 6±4 vs. 1±1, p<0.07), indicating that the variability was not due to inter-assay variation.

Conclusion

Among HLA-II subtypes, the DR antigen seems to be the most inducible, whereas DQ has a lower and more variable expression. The use of BOEC is breaking new in the analysis of HLA antigen expression in vitro. A better understanding of the expression of DSA ligand could be instrumental in our understanding of antibody-mediated rejection.