Expression of Immune-Related Genes and Possible Regulatory Mechanisms in Chronic Antibody-Mediated Rejection after...

Immune-related genes (IRGs) are pivotal in orchestrating immune infiltration processes. However, their expression patterns and potential regulatory pathways in patients with chronic antibody-mediated rejection (cABMR) post-kidney transplantation remain poorly understood. This study aimed to elucidate these aspects by analysing single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) derived from patients with cABMR and scrutinising cluster marker genes from PBMCs sourced from the ImmPort database to elucidate the underlying mechanisms.

PBMCs from patients with cABMR were examined using scRNA-seq to identify gene clusters, and IRG activity was quantified with the AUCell software package. Additionally, a bulk RNA sequencing dataset of kidney tissues was analysed to identify common IRGs between PBMCs and kidney tissue. Relevant regulatory transcription factors (TFs) were subsequently identified using the Human Transcription Factor Database. Finally, a protein-protein interaction network for key TFs was constructed using the STRING database.

We identified six distinct clusters of cells, namely, monocytes, neutrophils, myeloid cells, T cells, B cells and natural killer cells, with monocytes and neutrophils significantly elevated in patients with cABMR. These cells presented the highest IRG activity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the differentially expressed genes were primarily associated with immune responses. Sixteen common IRGs were identified in peripheral monocytes and kidney tissue, and 13 were identified in peripheral neutrophils and kidney tissue. Moreover, three key TFs (STAT1, IRF1 and FOS) associated with IRG expression were identified in these cells.

Our bioinformatic analysis of scRNA-seq and bulk RNA sequencing data suggests that peripheral monocytes and neutrophils may contribute to the inflammatory changes observed in cABMR. Furthermore, STAT1, IRF1 and FOS may play essential roles in the transcriptional regulation of IRGs in monocytes and neutrophils.