Multidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Public Hospitals of Paris (AP-HP), Sorbonne University, 75013 Paris, France; Public Hospitals of Paris (AP-HP), La Pitié-Salpêtrière Hospital, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), 75651 Paris, France; Sorbonne University, INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (i3), 75651 Paris, France.
Public Hospitals of Paris (AP-HP), La Pitié-Salpêtrière Hospital, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), 75651 Paris, France; Sorbonne University, INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (i3), 75651 Paris, France.
Anaesth Crit Care Pain Med. 2020 Feb;39(1):35-44. doi: 10.1016/j.accpm.2019.07.014. Epub 2019 Jul 30.
Acute respiratory distress syndrome (ARDS) is a common and fatal inflammatory condition. Whether T regulatory cells (Tregs) are beneficial or detrimental remains controversial, and longitudinal studies are lacking. Phenotyping of Tregs activation markers has been poorly reported. We aimed to evaluate quantitative and functional alterations in blood and bronchoalveolar Treg phenotype of ARDS patients.
We performed a single-centre observational study in a French intensive care unit. The study enrolled 60 ARDS and 45 non-ARDS patients. Patients under 18years old or with immunosuppression (native or acquired) were excluded. Tregs phenotypes were assessed by flow cytometry, while cytokines were measured by multiplex-based assays in blood and bronchoalveolar samples collected over 3weeks after the onset of ARDS.
Blood Tregs/CD4+ percentage (median %, 25-75% interquartile) was higher in ARDS patients than in non-ARDS patients: 12.1% [9.0-16.0] versus 9.9% [8.1-12.6], P=0.01. Alveolar Tregs/CD4+ percentage was lower in ARDS patients than in non-ARDS patients: 10.4% [6.3-16.6] versus 16.2% [12.4-21.1], P=0.03. In ARDS patients, Tregs activation was reduced in the blood and increased in the alveolus, compared to non-ARDS patients. ROC analysis revealed a threshold of 10.4% for the Tregs/CD4+ percentage in the blood collected within the first week of ARDS to discriminate between survivors and non-survivors (sensitivity: 75%; specificity 76%; area under the curve [95% confidence interval]: 0.72 [0.5-0.9]).
Quantitative and functional alterations in Treg phenotype were observed in patients with ARDS. Whether rebalancing Tregs phenotype with therapeutic interventions would be beneficial deserves further investigations.
急性呼吸窘迫综合征（ARDS）是一种常见且致命的炎症性疾病。调节性 T 细胞（Treg）是有益还是有害仍存在争议，且缺乏纵向研究。Treg 激活标志物的表型分析报道较少。我们旨在评估 ARDS 患者血液和支气管肺泡 Treg 表型的定量和功能变化。
我们在法国的一个重症监护病房进行了一项单中心观察性研究。该研究纳入了 60 例 ARDS 患者和 45 例非 ARDS 患者。年龄小于 18 岁或有免疫抑制（原发性或获得性）的患者被排除在外。通过流式细胞术评估 Treg 表型，通过基于多重检测的方法在 ARDS 发病后 3 周内采集的血液和支气管肺泡样本中测量细胞因子。
ARDS 患者血液中 Treg/CD4+的百分比（中位数，25-75% 四分位间距）高于非 ARDS 患者：12.1%[9.0-16.0]比 9.9%[8.1-12.6]，P=0.01。ARDS 患者肺泡中 Treg/CD4+的百分比低于非 ARDS 患者：10.4%[6.3-16.6]比 16.2%[12.4-21.1]，P=0.03。与非 ARDS 患者相比，ARDS 患者血液和肺泡中的 Treg 激活减少。ROC 分析显示，ARDS 发病后第 1 周内采集的血液中 Tregs/CD4+的百分比为 10.4%，可用于区分幸存者和非幸存者（敏感性：75%；特异性：76%；曲线下面积[95%置信区间]：0.72[0.5-0.9]）。
ARDS 患者的 Treg 表型出现了定量和功能改变。通过治疗干预来平衡 Treg 表型是否有益值得进一步研究。
