Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation

Dedeoğlu, Burç; Meijers, Ruud W. J.; Klepper, Mariska; Hesselink, Dennis A.; Baan, Carla C.; Litjens, Nicolle H.R.; Betjes, Michiel G. H.

doi:10.1111/ajt.13759

Cited by 9 publications

(6 citation statements)

References 45 publications

(69 reference statements)

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“…However, we could not show a relation between early post-transplantation infection risk and e.g. low numbers of naïve T cells [36]. In the current study, the thymic output in both the deceased and living group of recipients remained remarkably stable, indicating that even the most severely affected patients do not even partially restore their thymic function.…”

Section: Discussioncontrasting

confidence: 82%

A very low thymus function identifies patients with substantial increased risk for long-term mortality after kidney transplantation

et al. 2020

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Background: End-stage renal disease is associated with premature ageing of the T cell immune system but interindividual variation is substantial. The hypothesis was tested that advanced immunological T cell ageing assessed by peripheral T cell differentiation increases the long-term mortality risk after renal transplantation. Results: Circulating T cells of 211 recipients of a kidney from a living donor were analyzed before and in the first year after transplantation. The number of CD31-positive naive T cells (as a marker for recent thymic emigrants) and the differentiation status of the memory T cells was assessed. Thirty recipients died during follow-up of at least 5 years. Absolute numbers of naive CD4 + (living:258 cells/μl vs. deceased:101 cells/μl, p < 0.001) and naive CD8 + T cells (living:97 cells/μl vs. deceased:37 cells/μl, p < 0.001) were significantly lower in the deceased group prior to transplantation. In a multivariate proportional hazard analysis the number of naive CD4 + T cells remained associated with all-cause mortality (HR 0.98, CI 0.98-0.99, p < 0.001). The low number of naive T cells in the deceased patient group was primarily caused by a decrease in recent thymic emigrants (i.e. less CD31 + naive T cells) indicating a lowered thymus function. In addition, the physiological age-related compensatory increase in CD31 − naïve T cells was not observed. Within the first year after transplantation, the number and characteristics of naive T cells remained stable. Conclusions: A severe reduction in circulating naïve T cells because of a decrease in recent thymic emigrants is highly associated with all-cause mortality after renal transplantation.

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Section: Discussioncontrasting

confidence: 82%

A very low thymus function identifies patients with substantial increased risk for long-term mortality after kidney transplantation

et al. 2020

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“…The other hallmark of premature ageing is the decreased thymic output of naïve T cells in ESRD patients, which is much more than can be expected from the calendar age [7]. Some studies have associated a low number of naïve T cells to an increased risk for infection, although such a relation was not consistently found after transplantation [96]. Recently, we found that a very low thymic output of naïve T cells in recipients of a kidney transplant is highly associated with all-cause mortality at follow-up [54].…”

Section: Premature Ageing Of the Adaptive Immune System And Clinical mentioning

confidence: 99%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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Progressive loss of renal function is associated with a series of changes of the adaptive immune system which collectively constitute premature immunological ageing. This phenomenon contributes significantly to the mortality and morbidity of end-stage renal disease (ESRD) patients. In this review, the effect of ESRD on the T cell part of the adaptive immune system is highlighted. Naïve T cell lymphopenia, in combination with the expansion of highly differentiated memory T cells, are the hallmarks of immunological ageing. The decreased production of newly formed T cells by the thymus is critically involved. This affects both the CD4 and CD8 T cell compartment and may contribute to the expansion of memory T cells. The expanding populations of memory T cells have a pro-inflammatory phenotype, add to low-grade inflammation already present in ESRD patients and destabilize atherosclerotic plaques. The effect of loss of renal function on the thymus is not reversed after restoring renal function by kidney transplantation and constitutes a long-term mortality risk factor. Promising results from animal experiments have shown that rejuvenation of the thymus is a possibility, although not yet applicable in humans.

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“…This study was approved by the Medical Ethical Committee of the Erasmus MC (MEC-2007-228). The second dataset included recipients (n = 207) that participated in a randomized-controlled clinical trial with the primary aim to study the efficacy of a genotype-based approach to tacrolimus dosing [22]. All patients undergoing a living-donor kidney transplantation (KT) in the period from 1 November 2010 to 1 October 2013 were considered for participation in this study.…”

Section: Patientsmentioning

confidence: 99%

High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation

Betjes

Litjens

2020

PLoS ONE

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Background The hypothesis was tested that parameters of an aged T-cell compartment associate with the risk for late rejection after kidney transplantation. Methods Recipients of a kidney transplant in the period 2007-2013 were (N = 365) were included. T cells were characterized prior to transplantation by flow cytometry as naive (CD45RO-CCR7 +), central-memory (CD45RO + CCR7 +), effector-memory (CD45RO-CCR7-) or terminally differentiated CD8 + Temra (CD45RO-/CCR7-/CD28-) cells. T cell telomere length and thymic output were assessed prior to transplantation in 202 recipients. Follow-up was until December 2018. The date of the first time of biopsy-proven late rejection (>6 months after transplantation) was used to calculate the rejection-free survival time. Results Fifty cases of biopsy-proven rejection were recorded. Thymic output and T cell telomere length did not associate with late rejection-free survival. However, the percentage and absolute numbers of CD8 + Temra and CD28null CD8 + T cells were significantly lower in patients with late rejection. Specifically, in the highest tertile of percentages of CD28null CD8 + T cells, the cumulative incidence of late rejection at 5 and 10 years was only 5% and 8% compared to 16% and 20% in the middle to lowest tertile (p = 0.002). Multivariate proportional hazard analysis showed that percentage and absolute number of CD28null CD8 + T cells remained significantly associated with late rejection and rejection-related graft loss. Conclusion High numbers of differentiated CD28null CD8 + T cells decrease the risk for late rejection and rejection-related graft loss after kidney transplantation.

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Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation

Cited by 9 publications

References 45 publications

A very low thymus function identifies patients with substantial increased risk for long-term mortality after kidney transplantation

A very low thymus function identifies patients with substantial increased risk for long-term mortality after kidney transplantation

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation

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