Introduction: Antibody-mediated rejection (ABMR) is the leading cause of future graft loss. A comprehensive understanding of the immune landscape in ABMR is still lacking. Here, we aimed to define the transcriptomic landscape of ABMR at single-cell resolution by using single-cell RNA sequencing (scRNA-seq).

Method: Single-cell transcriptomes from one acute antibody-mediated rejection (AMR) biopsy sample was generated. Single-cell transcriptomes of a healthy adult kidney and a chronic antibody-mediated rejection (CAMR) biopsy sample were obtained from the public databases. Unsupervised clustering analysis was employed to identify cell types of the biopsy specimens. Gene set enrichment analysis (GSEA) was used to explore functional differences. Intracellular and intercellular communication pathways were performed to find crosstalk between cell subpopulations.

Results: A higher proportion of endothelial cells was found in the CAMR group. The AMR group had a higher proportion of plasma cells and T/NK cells. The overexpressed genes in rejection group were mainly involved in inflammatory signaling pathways and rejection-related pathways. Compared with the control group, M1-like subtype macrophages were increased in the rejection group. Our results also showed that macrophages/dendritic cells and endothelial cells possessed the most interaction pairs with other immune cells, especially in the AMR group.

Conclusion: Our study provides new insights into AMR and offers a reliable reference for studies on ABMR in kidney transplantation.