The Evolution of Molecular Phenotypes Through Time in Kidney Transplant Recipients

The correlation between histologic lesions and allograft gene expression data is a subject of significant interest. Most analyses include a single for-cause biopsy from each recipient, precluding serial assessment of gene scores.

Using the nCounter system, we evaluated the Banff Human Organ Transplant gene panel in a unique cohort of 8 renal transplant recipients, each with 3 distinct histologic phenotypes (no rejection, T cell-mediated rejection [TCMR], and antibody-mediated rejection [AMR]), to explore the serial evolution of molecular phenotypes.

No rejection biopsies showed large interindividual differences in TCMR and AMR gene scores. Compared with biopsies with No Rejection, TCMR gene scores were greater in those with TCMR (mean fold change 1.95 ± 0.87, P = 0.0174). Similarly, compared with biopsies with No rejection, gene scores for AMR (mean fold change 1.43 ± 0.24, P = 0.0002), donor-specific antibody selective transcripts (mean fold change 1.33 ± 0.22, P = 0.002), and endothelial cell-associated transcripts (mean fold change 1.17 ± 0.06, P = 0.04) were greater at the time of AMR.

In most cases, deviations in gene scores occurred in the expected direction as recipients transitioned through histologic phenotypes. The unexpected deviations in gene scores and the significant variability among individuals within histologic phenotypes warrant further investigation.