CD4⁺CD25⁺CD39⁺ Regulatory T Cells as Novel Diagnostic Biomarkers for Catheter‐Related Bloodstream Infections in Hemodialysis Patients

Introduction Catheter‐related bloodstream infections (CRBSI) represent a major cause of morbidity and mortality in hemodialysis (HD) patients. Current diagnostic reliance on blood cultures leads to delays in treatment initiation, underscoring the need for rapid biomarkers. Emerging evidence suggests that CD4 + CD25 + CD39 + regulatory T cells (Tregs) may serve as indicators of immune dysregulation during CRBSI. This study aimed to: (1) evaluate CD4 + CD25 + CD39 + Tregs as diagnostic biomarkers for CRBSI in HD patients, (2) compare the reliability of dialysis bloodline cultures versus peripheral venipuncture cultures, and (3) determine optimal fever thresholds for CRBSI prediction. Methods In this prospective cohort study, we enrolled 87 HD patients with suspected CRBSI (42 confirmed CRBSI, 45 non‐CRBSI controls). Treg frequencies were quantified using flow cytometry. Paired blood cultures were obtained simultaneously from dialysis bloodlines and peripheral veins. CRBSI was confirmed using CDC criteria (≥ 3‐fold higher colony count or ≥ 2‐h earlier positivity in catheter‐derived cultures). Findings CRBSI patients showed markedly elevated Treg frequencies (14.1% ± 4.5% vs. 3.3% ± 2.8%, p < 0.001) with outstanding diagnostic accuracy (AUC 0.974, 98.3% sensitivity, 96.3% specificity). Dialysis bloodline cultures demonstrated excellent concordance with peripheral cultures (92% agreement, κ = 0.88). Fever > 38.0°C strongly predicted CRBSI (OR 18.67, p < 0.001; 85% specificity). The diagnostic triad of Tregs > 10%, CRP > 50 mg/L, and fever > 38.0°C achieved exceptional discrimination (AUC 0.93). Discussion CD4 + CD25 + CD39 + Tregs represent a novel, high‐performance biomarker for CRBSI. Combined with validated dialysis line cultures and fever thresholds, they enable rapid diagnosis and early intervention, offering a practical alternative to current culture‐dependent approaches in hemodialysis patients.