Cell-Specific Expression of Class II HLA Genes in Rejecting Kidney Transplant Biopsies by Single-Cell RNAseq
- Transplantation: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 2101 Transplantation: Basic
- Malone, Andrew F., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
- Leckie-Harre, Aidan, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
- Nunna, Venkatrao, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
- Humphreys, Benjamin D., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
- Liu, Chang, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
Antibody-mediated rejection (AMR) remains one of the major causes of allograft failure. Anti-HLA antibody binding to endothelial cells is thought to be a central event driving AMR. Expression of both alpha and beta chains encoded by class II HLA genes is required for complete HLA class II protein expression on the cell surface.
We determined the expression of HLA-DR and HLA-DQ genes from single cells from two datasets of human kidney transplant biopsies. The proportion of cells expressing both alpha and beta chains for HLA-DR (DRA/DRB1, or DRab hereafter) and for HLA-DQ (DQA1/DQB1 or DQab hereafter) was determined across all rejection phenotypes. The gene expression pattern in endothelial cells with DRab or DQab was compared to that of endothelial cells not expressing DRab or DQab.
We analyzed two datasets for this study: A) 81139 cells from 5 biopsies (AMR or no-rejection) published previously, and B) new data of 31,203 cells from 11 biopsies (no-rejection, AMR, TCMR or mixed). In dataset A, DQab expression was restricted to endothelial cells (EC) and immune cells with little expression in other cells of the kidney. DRab was widely expressed in all cell types. Similar profiles were found in dataset B (fig1a+b). In EC, PLA1A, a molecular marker for AMR, showed a significantly increased expression in EC positive for DQab or DRab when compared to EC negative for DQab/DRab (fig1c+d).
Cell specific class II HLA gene expression can be determined from single-cell RNAseq data. Expression of DQab/DRab in ECs is associated with molecular markers for AMR, which may provide diagnostic and mechanistic insight for AMR.
- NIDDK Support