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

Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients

Background. The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via “inflamm-aging.” Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes. Methods. Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression. Results. Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16−) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients. Conclusions. In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation