T-cell receptor Vβ repertoire skewing reflects premature immune senescence in children with chronic kidney disease


Ulgen E., SAYGILI S. K., KIYKIM A., BURTECENE N., Yilmaz E. K., AĞBAŞ A., ...More

PEDIATRIC NEPHROLOGY, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2026
  • Doi Number: 10.1007/s00467-026-07267-w
  • Journal Name: PEDIATRIC NEPHROLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE
  • Istanbul University Affiliated: No

Abstract

BackgroundChronic kidney disease (CKD), characterized by chronic inflammation and uremic toxicity, represents a state of premature immune aging. However, data on T-cell receptor (TCR) repertoire alterations in pediatric CKD are limited. The TCR variable beta (V beta) region defines distinct T-cell subfamilies generated by V(D)J recombination and reflects T-cell repertoire diversity and clonal composition. Alterations in TCR V beta distribution indicate repertoire remodeling associated with chronic antigenic stimulation and immune aging beyond quantitative lymphocyte changes. This study aimed to characterize TCR V beta family repertoire in children with advanced CKD and explore their associations with clinical and biochemical parameters.MethodsIn this single-center, cross-sectional study, 35 children with CKD stages 3b-5 (21 non-dialysis, 14 dialysis) and 15 age- and sex-matched healthy controls were enrolled. Peripheral blood lymphocyte subsets and TCR V beta 1-V beta 23 distributions were assessed by flow cytometry and compared with clinical and laboratory measures. Group comparisons were performed using the Mann-Whitney U test, and associations were assessed using Spearman correlation analysis.ResultsChildren with CKD exhibited a skewed TCR V beta repertoire, with reduced expression of V beta 9 and V beta 11 and increased V beta 17 (p = 0.041, 0.001, 0.014, respectively) with corresponding moderate-to-large effect sizes (r = 0.37, r = 0.61, and r = 0.44). Dialysis patients showed lower V beta 11 and higher V beta 12 expression compared with non-dialysis patients (p = 0.034 and p = 0.048), with large effect sizes (r = 0.68 and r = 0.66). Reduced V beta 9 correlated with low BMI and higher proteinuria, and reduced V beta 11 correlated with hypoalbuminemia, whereas elevated V beta 12 was associated with higher CRP and creatinine levels. Total lymphocyte counts were preserved, although dialysis patients demonstrated a higher CD4/CD8 ratio.ConclusionsPediatric CKD is associated with selective and non-uniform remodeling of the T-cell repertoire, reflecting premature immune senescence. The associations between TCR V beta alterations, inflammation, and nutritional markers suggest synergistic effects of uremic toxicity and protein-energy imbalance on immune aging, warranting larger mechanistic studies.Graphical AbstractA higher resolution version of the Graphical abstract is available as Supplementary information.