629. Blood Transcriptome Variations Predict Infection and Rejection in the Older Kidney Transplant Recipient
Session: Poster Abstract Session: Pathogenesis and Immune Response
Thursday, October 4, 2018
Room: S Poster Hall
Background: Compared to 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.

Objective: Evaluate older versus younger solid organ transplant recipients for differential patterns of gene expression associated with infection and rejection.

Methods: Peripheral 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..

Results: Genes 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.

Conclusion: Differential 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.

Joanna Schaenman, MD PhD1, Maura Rossetti, PhD2, Suphamai Bunnapradist, MD PhD3, Emily Liang, BA4, Omer Beaird, MD5, Elaine Reed, PhD2 and Steve Cole, PhD6, (1)Division of Infectious Diseases, University of California, Los Angeles, Los Angeles, CA, (2)David Geffen School of Medicine at UCLA, Department of Pathology, Los Angeles, CA, (3)David Geffen School of Medicine, Division of Nephrology, Los Angeles, CA, (4)David Geffen School of Medicine, Los Angeles, CA, (5)Medicine - Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, (6)David Geffen School of Medicine, Division of Geriatrics, Los Angeles, CA

Disclosures:

J. Schaenman, None

M. Rossetti, None

S. Bunnapradist, None

E. Liang, None

O. Beaird, None

E. Reed, None

S. Cole, None

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