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

); Psychosom Med

Abstract Objective-To examine the association between the experience of daily interpersonal stress and levels of C-reactive protein (CRP), an inflammatory marker that is a key indicator of cardiovascular risk, during the teenage years. Methods-A total of 69 adolescents (M age = 17.78 years) completed daily diary checklists each night for 14 days in which they reported their experience of negative interpersonal interactions in the domains of family, peers, and school (e.g., conflict with family and friends, peer harassment, punishment by parents and teachers). Blood samples were obtained an average of 8.63 months later and assayed for circulating levels of CRP, using enzyme-linked immunosorbent assay. Measures of body mass index (BMI), socioeconomic status (SES), substance use, stressful life events, rejection sensitivity, and psychological distress were obtained. Results-A greater frequency of daily interpersonal stress was associated with higher levels of CRP, even after controlling for BMI, SES, substance use, life events, rejection sensitivity, psychological distress, and frequency of daily interpersonal stress 2 years earlier. Conclusions-Experiencing a high frequency of interpersonal stressors that are typical of adolescent life is associated with higher levels of inflammation even among a normative, healthy sample of adolescents. Additional work should focus on other daily experiences during the adolescent period and their implications for elevated risk for later cardiovascular disease