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Abstract: FR-OR123

Single Cell RNA Sequencing of Antibody-Mediated Rejection and Control Kidney Transplant Biopsies Reveals Endothelial, T-Cell, and Monocyte Intercellular Communication and Host-Donor Chimerism

Session Information

Category: Transplantation

  • 1901 Transplantation: Basic


  • Malone, Andrew F., Washington University School of Medicine, Clayton, Missouri, United States
  • Wu, Haojia, Washington University School of Medicine, Clayton, Missouri, United States
  • Chadha, Ashima, Washington University School of Medicine, Clayton, Missouri, United States
  • Humphreys, Benjamin D., Washington University School of Medicine, Clayton, Missouri, United States

Antibody mediated rejection (AMR) is one of the major causes of allograft failure yet current treatment strategies are suboptimal reflecting our poor understanding of this disease. We performed single cell(sc)RNAseq on biopsies from patients with AMR and compared them to non-AMR biopsies.


The 10X platform was used for library preparation. Sequencing depth was ~50k reads/cell. CellRanger, R and Seurat were used to make gene-cell matrices and for downstream analyses. Donor and recipeint exome sequencing was also performed. IRB approved.


96,547 cells (avg=1292 genes detected/cell) from 7 kidney transplant biopsies were included in the integrated analysis using UMAP. 21 cell clusters were identified and included all major tubular types (PT,LOH,PC,IC), stroma, endothelium, lymphocytes (T and B cells) and monocytes (figure). In AMR biopsies, monocytes expressed the B cell activator BAFF and B cells upregulated expression of its cognate receptors TACI and BMCA, suggesting monocyte driven B cell activation. Endothelial cells in AMR showed increased expression of cytokines that recruit T cells such as CXCL9, as well as the chemokine receptor ACKR1, suggesting that endothelial cells amplify the immune response. Of note, we could distinguish host from donor leukocytes based on expressed SNVs defined by exome sequencing. Whether donor-derived leukocytes exhibit differential gene expression compared to their host counterparts is under analysis.


Comprehensive scRNAseq of human AMR suggests that monocytes drive B cell activation and that endothelial cells recruit T cells. We also show, for the first time, that donor leukocytes persist even years after transplantation. Whether donor-derived leukocytes differentially regulate AMR represents a new and potentially important direction in transplantation research enabled by scRNAseq.


  • NIDDK Support