Differences in Gene Expression in Older Compared With Younger Kidney Transplant Recipients

BACKGROUND: For the growing numbers of older transplant patients, increased incidence of infection and death compared with younger patients may limit the many benefits provided by transplantation. However, little is known about age-associated immune dysfunction in the older transplant recipient. METHODS: A cohort of 60 kidney transplant recipients, 23 older (≥ 60y) and 37 younger (30-59y), matched on antithymocyte induction and donor type (living vs deceased) was evaluated. Gene expression in peripheral blood mononuclear cells 3 months after kidney transplantation was analyzed to compare differences between older and younger patients. RESULTS: Proinflammatory genes were upregulated in older kidney transplant patients, including cytokines IL1-β and IL-6. Downregulated genes were associated with B-cell and T-cell function, including CCR7 and CD27. Analysis of predicted transcription factor binding suggested an increase in proinflammatory transcription factor CCAAT/enhancer binding protein β-binding sites in older patients, whereas interferon regulatory factor 2 transcription factor binding sites were less prevalent. CONCLUSIONS: Older kidney transplant recipients exhibited multiple differences in gene expression compared with younger patients, with upregulation of proinflammatory genes and downregulation of adaptive immune response genes. These findings may explain the mechanism of increased vulnerability to infection and malignancy observed in older transplant patients.