Dataset Information

End stage renal disease patients have a skewed T cell receptor V? repertoire.

ABSTRACT:

Background

End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) V? repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR V? repertoire was assessed.

Results

A higher proportion of ESRD patients (68.9 %) had a skewed TCR V? repertoire compared to age and cytomegalovirus (CMV) - IgG serostatus matched healthy individuals (31.4 %, P?ConclusionsESRD significantly skewed the TCR V? repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity.

SUBMITTER: Huang L

PROVIDER: S-EPMC4681023 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

End stage renal disease patients have a skewed T cell receptor Vβ repertoire.

Huang Ling L Langerak Anton W AW Wolvers-Tettero Ingrid L M IL Meijers Ruud W J RW Baan Carla C CC Litjens Nicolle H R NH Betjes Michiel G H MG

Immunity & ageing : I & A 20151214

<h4>Background</h4>End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed.<h4>Results</h4>A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) - IgG serostatus matched healthy individuals (31.4 %, P < 0.001). Ag ...[more]

PMID: 26677394

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Project description:A broad T cell receptor (TCR-) repertoire is required for an effective immune response. TCR-repertoire diversity declines with age. End-stage renal disease (ESRD) patients have a prematurely aged T cell system which is associated with defective T cell-mediated immunity. Recently, we showed that ESRD may significantly skew the TCR V?-repertoire. Here, we assessed the impact of ESRD on the TCR V?-repertoire within different T cell subsets using a multiparameter flow-cytometry-based assay, controlling for effects of aging and CMV latency. Percentages of 24 different TCR V?-families were tested in circulating naive and memory T cell subsets of 10 ESRD patients and 10 age- and CMV-serostatus-matched healthy individuals (HI). The Gini-index, a parameter used in economics to describe the distribution of income, was calculated to determine the extent of skewing at the subset level taking into account frequencies of all 24 TCR V?-families. In addition, using HI as reference population, the differential impact of ESRD was assessed on clonal expansion at the level of an individual TCR V?-family. CD8+, but not CD4+, T cell differentiation was associated with higher Gini-TCR indices. Gini-TCR indices were already significantly higher for different CD8+ memory T cell subsets of younger ESRD patients compared to their age-matched HI. ESRD induced expansions of not one TCR V?-family in particular and expansions were predominantly observed within the CD8+ T cell compartment. All ESRD patients had expanded TCR V?-families within total CD8+ T cells and the median (IQ range) number of expanded TCR V?-families/patient amounted to 2 (1-4). Interestingly, ESRD also induced clonal expansions of TCR V?-families within naive CD8+ T cells as 8 out of 10 patients had expanded TCR V?-families. The median (IQ range) number of expanded families/patient amounted to 1 (1-1) within naive CD8+ T cells. In conclusion, loss of renal function skews the TCR V?-repertoire already in younger patients by inducing expansions of different TCR V?-families within the various T cell subsets, primarily affecting the CD8+ T cell compartment. This skewed TCR V?-repertoire may be associated with a less broad and diverse T cell-mediated immunity.

Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.