Older transplant recipients experience increased rates of death and infection as compared with younger patients. Our previous studies demonstrated increased frequency of terminally differentiated and exhausted T cells in older transplant recipients. We hypothesized that increased transcription of pro-inflammatory genes would explain the mechanism behind the immunologic changes observed.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 60 kidney transplant recipients 3 months post-transplant in an IRB-approved study. The 24 elderly and 36 non-elderly patients were matched on transplant type and induction immunotherapy. Patients received protocolized immunosuppression regimens independent of patient age. 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. Data analysis was performed using R.

Results: Gene expression analysis evaluated 34,674 individual gene transcripts. At a threshold of 1.25-fold increase or decrease, 135 genes were upregulated and 35 genes downregulated in older as compared with younger patients. In the older patients, bioinformatics characterizing the nature of differentially expressed genes revealed a strong over-representation of inflammatory genes and an underrepresentation of genes associated with the Type I interferon antiviral immune response.

Conclusion: Despite receiving identical immunosuppression regimens and matching on donor type, induction type, and sex, older kidney transplant recipients displayed significantly different patterns of gene expression with up-regulation of inflammatory genes and down-regulation of interferon-related genes as compared with younger patients. This suggests a mechanism for dysfunctional immune phenotypes and the increased incidence of infection and death, but less rejection observed in older patients. Transcripts most predictive of immunologic exhaustion may be candidates for biomarkers to allow customization of immunosuppression regimens in older patients, preventing adverse outcomes.

CITATION INFORMATION: Schaenman J, Beiard O, Liang E, Sidwell T, Groysberg V, Rosetti M, Abdalla B, Lum E, Bunnapradist S, Pham T, Dannovitch G, Veale J, Gritsch H, Karlamangla A, Cole S, Reed E. Increased Pro-Inflammatory and Decreased Interferon-Related Gene Expression in Older as Compared with Younger Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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