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Abstract: PO2051

Circulating Donor-Specific Anti-HLA Antibodies Induce Immune Activation Independent of Kidney Transplant Histopathological Findings

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Van Loon, Elisabet, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Lamarthee, Baptiste, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Senev, Aleksandar, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Emonds, Marie-Paule, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Van Craenenbroeck, Amaryllis H., Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Thaunat, Olivier, Edouard Herriot Hospital Lyon, Lyon, France
  • Naesens, Maarten, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
Background

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated.

Methods

Levels of 28 cytokines were assessed using multiplexed Luminex testing in 293 peripheral blood samples, collected at time of a kidney allograft biopsy for graft dysfunction within the first year after transplantation in a cohort of 192 consecutive transplants at a single kidney transplant center.

Results

Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels (Figure a, cluster 2). This patient subset (N=20) was hallmarked by high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) (Figure b) and histological rejection (70%), and had worse graft survival compared to the group with low cytokine levels (N= 172, HLA-DSA in 1.7% and rejection in 33.7%). Serum C-reactive protein and polyomavirus and/or CMV viremia did not differ between the two clusters. Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Single-cell RNAseq analysis on public data from kidney transplant biopsies demonstrated expression of these cytokines in endothelial cells, non-classical monocytes and natural killer cells. We confirmed the inflammatory cytokine profiles in in vitro models of HLA-DSA-mediated crosstalk between endothelial cells, NK cells and monocytes.

Conclusion

The expression of pro-inflammatory cytokines is increased in peripheral blood of kidney transplant patients with circulating HLA-DSA, even in the absence of histopathology of rejection. These results challenge the vision that kidney transplant histology is the gold standard for identification of ongoing allo-immune processes.