Yu Zhi-xin, Ji Mu-sen, Yan Jun, Cai Yan, Liu Jing, Yang Hong-feng, Li Yong, Jin Zhao-chen, Zheng Jin-Xu
Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China.
Department of Respiratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
Crit Care. 2015 Mar 11;19(1):82. doi: 10.1186/s13054-015-0811-2.
Recent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS.
This prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment.
Within 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO₂/FiO₂. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001).
The Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.
最近的研究表明，由CD4+ T细胞介导的肺部炎症可能促成急性呼吸窘迫综合征（ARDS）的发病机制。在许多不同的炎症和自身免疫性疾病中，已发现CD4+CD25+Foxp3+调节性T（Treg）细胞与辅助性T（Th）17细胞之间存在失衡，而Th17/Treg平衡在ARDS中的作用仍 largely未知。本研究的目的是调查ARDS患者的Th17/Treg模式及其对疾病严重程度和预后的影响。
这项前瞻性观察性研究纳入了79例符合ARDS柏林定义的患者和26例年龄及性别匹配的健康对照。通过流式细胞术分析循环中Th17和Treg细胞频率，并采用酶联免疫吸附测定（ELISA）法检测血清中Th17和Treg相关细胞因子的表达。在入组时还计算急性生理与慢性健康状况评估（APACHE）II评分、序贯器官衰竭评估（SOFA）评分和肺损伤评分。
在ARDS发病后24小时内，外周循环中Th17和Treg细胞频率的变化从轻度ARDS到重度ARDS逐渐增加。Th17/Treg比值与APACHE II评分、SOFA评分和肺损伤评分呈正相关，而与PaO₂/FiO₂呈负相关。Th17/Treg比值预测ARDS患者28天死亡率的受试者工作特征（AUC）曲线下面积高于APACHE II评分、SOFA评分、肺损伤评分以及PaO2/FiO2。使用>0.79的Th17/Treg比值临界值来确定28天死亡率，敏感性为87.5%，特异性为68.1%。多因素逻辑回归显示，Th17/Treg比值>0.79（比值比=8.68，P=0.002）是ARDS患者28天死亡率的独立预测因素。最后，Th17/Treg比值>0.79和≤0.79的患者在28天随访时的累积生存率也有显著差异（P<0.001）。
有利于Th17偏移的Th17/Treg失衡代表了减轻肺损伤的潜在治疗靶点和早期ARDS患者的新型风险指标。
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