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

BACKGROUND: Chronic 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 (Vβ) region defines distinct T-cell subfamilies generated by V(D)J recombination and reflects T-cell repertoire diversity and clonal composition. Alterations in TCR Vβ distribution indicate repertoire remodeling associated with chronic antigenic stimulation and immune aging beyond quantitative lymphocyte changes. This study aimed to characterize TCR Vβ family repertoire in children with advanced CKD and explore their associations with clinical and biochemical parameters. METHODS: In 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 Vβ1-Vβ23 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. RESULTS: Children with CKD exhibited a skewed TCR Vβ repertoire, with reduced expression of Vβ9 and Vβ11 and increased Vβ17 (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 Vβ11 and higher Vβ12 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 Vβ9 correlated with low BMI and higher proteinuria, and reduced Vβ11 correlated with hypoalbuminemia, whereas elevated Vβ12 was associated with higher CRP and creatinine levels. Total lymphocyte counts were preserved, although dialysis patients demonstrated a higher CD4/CD8 ratio. CONCLUSIONS: Pediatric CKD is associated with selective and non-uniform remodeling of the T-cell repertoire, reflecting premature immune senescence. The associations between TCR Vβ alterations, inflammation, and nutritional markers suggest synergistic effects of uremic toxicity and protein-energy imbalance on immune aging, warranting larger mechanistic studies.