629. Blood Transcriptome Variations Predict Infection and Rejection in the Older Kidney Transplant Recipient

Abstract

BackgroundCompared with younger patients on similar immunosuppression regimens, older solid-organ transplant recipients experience increased rates of infection and death, but decreased rates of rejection. Our previous findings demonstrated increased T-cell immunosenescence and pro-inflammatory monocytes in older patients. This study sought to define the implications of transcriptome alterations for clinical outcomes. The objective of this abstract is to evaluate older vs. younger solid-organ transplant recipients for differential patterns of gene expression associated with infection and rejection.MethodsPeripheral blood mononuclear cells were isolated from 23 older (≥age 60) and 37 matched younger (ages 30–59) kidney transplant recipients at 3 months after transplantation. RNA extraction was performed on banked PBMCs. Isolated RNA was converted to fluorescent cRNA and hybridized to Illumina Human HT-12 v4 BeadArrays. Gene expression values were quantile-normalized and log2-transformed for mixed effect linear model analyses to identify differential expression as a function of age, adjusted for induction type, donor type, and sex. Statistical analysis was performed using R software.ResultsGenes differentially expressed in older patients revealed an over-representation of pro-inflammatory genes and a down regulation of genes associated with the CD8 immune response. Patients who went on to develop infection demonstrated an increase in IRF transcription factor activation and plasmacytoid dendritic cell activity. Patients who developed rejection demonstrated an increase in myeloid lineage immune cell activity.ConclusionDifferential patterns of gene expression were observed in patients who developed infection in the first year after kidney transplantation. These findings were distinct from the gene expression changes associated with development of rejection. These findings may explain the mechanism behind vulnerability to infection in older transplant patients. In addition, monitoring of changes in gene expression may provide an avenue for patient monitoring after transplantation as well as individualization of immune suppression after solid-organ transplantation.Disclosures All authors: No reported disclosures.