Comparison of Rejection-Specific Genes in Peripheral Blood and Allograft Biopsy From Kidney Transplant.

BACKGROUND: Although improved understanding and assessment of organ rejection significantly contribute to long-term allograft survival after kidney transplantation, reliable and predictive biomarkers that enable diagnoses of rejection state are lacking. Patient rejection of a kidney graft displays a specific blood and biopsy transcriptional pattern, raising the question of whether transcript biomarkers in blood could reflect events within the allograft.

METHODS: Differential expression genes were screened on large-scale transcriptomic data from blood and allograft biopsies, which included recipients undergoing rejection and recipients with stable renal function.

RESULTS: We found that the number of rejection-related genes in biopsy samples was much greater than in blood. We observed only one overlapping gene, HIST1H4A, consistently expressed in biopsy samples and blood. Functional association of the identified genes in biopsies implicated a strong involvement of inflammatory-immune pathways. Rejection-related genes in the mammalian target of rapamycin-signaling pathway were down-regulated, and genes related to allograft rejection and graft-versus-host disease were up-regulated in allograft biopsy samples. We also recognized the core signaling elements (PIK3R2 and EGFR) in inflammatory-immune pathways based on biopsy samples.

CONCLUSIONS: We have expanded our understanding of rejection-specific gene expression pattern in allograft biopsy and peripheral blood, and provided a candidate set of overlapping genes for screening of rejection in kidney transplant recipients.