Hesham Kamal Habeeb Keryakos, Christina Rafat Kamal, Aliaa Mohamed Monir Higazi
{"title":"CD4+CD25+CD39+调节性T细胞作为血液透析患者导管相关血流感染的新诊断生物标志物","authors":"Hesham Kamal Habeeb Keryakos, Christina Rafat Kamal, Aliaa Mohamed Monir Higazi","doi":"10.1111/hdi.70021","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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<sup>+</sup>CD25<sup>+</sup>CD39<sup>+</sup> regulatory T cells (Tregs) may serve as indicators of immune dysregulation during CRBSI. This study aimed to: (1) evaluate CD4<sup>+</sup>CD25<sup>+</sup>CD39<sup>+</sup> 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.</p><p><strong>Methods: </strong>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).</p><p><strong>Findings: </strong>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).</p><p><strong>Discussion: </strong>CD4<sup>+</sup>CD25<sup>+</sup>CD39<sup>+</sup> 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.</p>","PeriodicalId":94027,"journal":{"name":"Hemodialysis international. 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Emerging evidence suggests that CD4<sup>+</sup>CD25<sup>+</sup>CD39<sup>+</sup> regulatory T cells (Tregs) may serve as indicators of immune dysregulation during CRBSI. This study aimed to: (1) evaluate CD4<sup>+</sup>CD25<sup>+</sup>CD39<sup>+</sup> 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.</p><p><strong>Methods: </strong>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).</p><p><strong>Findings: </strong>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).</p><p><strong>Discussion: </strong>CD4<sup>+</sup>CD25<sup>+</sup>CD39<sup>+</sup> Tregs represent a novel, high-performance biomarker for CRBSI. 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引用次数: 0
摘要
导述：导管相关性血流感染（CRBSI）是血液透析（HD）患者发病和死亡的主要原因。目前对血液培养的诊断依赖导致了治疗开始的延迟，强调了对快速生物标志物的需求。新出现的证据表明，CD4+CD25+CD39+调节性T细胞（Tregs）可能是CRBSI期间免疫失调的指标。本研究旨在：(1)评估CD4+CD25+CD39+ Tregs作为HD患者CRBSI的诊断生物标志物，(2)比较透析血培养与外周静脉穿刺培养的可靠性，以及(3)确定预测CRBSI的最佳发热阈值。方法：在这项前瞻性队列研究中，我们招募了87例疑似CRBSI的HD患者（42例确诊CRBSI， 45例非CRBSI对照）。流式细胞术定量Treg频率。同时从透析血液系和外周静脉获得配对血培养。CRBSI采用CDC标准确诊（集落计数≥3倍或导管培养≥2小时早期阳性）。结果：CRBSI患者Treg频率明显升高（14.1%±4.5% vs. 3.3%±2.8%），p 38.0°C强烈预测CRBSI (OR 18.67, p 10%), CRP > 50 mg/L，发热> 38.0°C具有特殊区别（AUC 0.93）。讨论：CD4+CD25+CD39+ treg代表了一种新的、高性能的CRBSI生物标志物。与有效的透析培养和发热阈值相结合，它们能够快速诊断和早期干预，为血液透析患者提供了一种替代目前依赖培养方法的实用方法。
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.
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