TSPO and LRBA Expression Is Associated with Acute Renal Allograft Rejection: An Integrative Transcriptomic Analysis

Acute renal transplant rejection causes allograft injury and affects long-term graft survival. Mitophagy helps maintain mitochondrial homeostasis and regulate immune function, but its relationship with acute rejection remains unclear. We integrated public renal allograft transcriptomic datasets using differential expression analysis, weighted gene co-expression network analysis, and machine learning. We performed external cohort validation, survival analysis, immune deconvolution, single-cell RNA sequencing analysis, virtual knockout analysis, and quantitative PCR in mouse renal allografts. Among 32 shared mitophagy-associated genes which we identified, TSPO was consistently upregulated and LRBA was downregulated across independent biopsy cohorts. An exploratory TSPO/LRBA two-gene model showed modest discrimination between rejection and non-rejection samples. Higher model scores were associated with poorer graft survival. An exploratory analysis of the model was then performed in peripheral blood. Functional and single-cell analyses linked these genes to monocyte/macrophage populations, antigen presentation, T-cell signaling, and inflammatory pathways. Virtual knockout analysis predicted changes in antigen presentation, phagocytosis, and allograft rejection pathways. Quantitative PCR confirmed increased TSPO and decreased LRBA expression in mouse renal allografts with acute rejection. Together, these findings identify TSPO and LRBA as new candidate mitophagy-associated biomarkers linked to monocytes/macrophages and support further investigation of their associations with acute renal transplant rejection.