Abstract
Background: A previously proposed immune risk profile (IRP), based on T cell phenotype and CMV serotype, is associated with mortality in the elderly and increased infections post-kidney transplant. To evaluate if NK cells contribute to the IRP and if the IRP can be predicted by a clinical T cell functional assays, we conducted a cross sectional study in renal transplant candidates to determine the incidence of IRP and its association with specific NK cell characteristics and ImmuKnow® value.Material and Methods: Sixty five subjects were enrolled in 5 cohorts designated by age and dialysis status. We determined T and NK cell phenotypes by flow cytometry and analyzed multiple factors contributing to IRP.Results: We identified 14 IRP+ [CMV seropositivity and CD4/CD8 ratio < 1 or being in the highest quintile of CD8+ senescent (28CD–/CD57+) T cells] individuals equally divided amongst the cohorts. Multivariable linear regression revealed a distinct IRP+ group. Age and dialysis status did not predict immune senescence in kidney transplant candidates. NK cell features alone could discriminate IRP– and IRP+ patients, suggesting that NK cells significantly contribute to the overall immune status in kidney transplant candidates and that a combined T and NK cell phenotyping can provide a more detailed IRP definition. ImmuKnow® value was negatively correlated to age and significantly lower in IRP+ patients and predicts IRP when used alone or in combination with NK cell features.Conclusion: NK cells contribute to overall immune senescence in kidney transplant candidates.
Highlights
The number of elderly end stage renal disease (ESRD) patients in the United States continues to grow [1], as does the number of elderly patients listed for kidney transplant [2, 3]
There were no significant differences between the study groups except for their age and the group with
We evaluated if enhanced proportions of Natural killer (NK) cells with phenotypic features reflecting terminal differentiation are associated with CMV serostatus, age, kidney disease, and dialysis in our cohort of renal transplant candidates
Summary
The number of elderly end stage renal disease (ESRD) patients in the United States continues to grow [1], as does the number of elderly patients listed for kidney transplant [2, 3]. Immune Senescence in Kidney Transplant Candidates of allograft rejection; they are at an increased risk for infectious complications after transplant. Changes in T-cell phenotype and function known as T-cell senescence have been associated with mortality in the elderly [14], increased risk of infection [15, 16], and cardiovascular disease [17, 18]. An immune risk profile (IRP) has been proposed which has been associated with increased infectious complications posttransplant and mortality in the elderly [32,33,34]. A previously proposed immune risk profile (IRP), based on T cell phenotype and CMV serotype, is associated with mortality in the elderly and increased infections post-kidney transplant. To evaluate if NK cells contribute to the IRP and if the IRP can be predicted by a clinical T cell functional assays, we conducted a cross sectional study in renal transplant candidates to determine the incidence of IRP and its association with specific NK cell characteristics and ImmuKnow® value
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