title: The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. 9yzx@163.com.
authors.forename: Zhi-xin
authors.initials: ZX
authors.lastname: Yu
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. jimusen@163.com.
authors.forename: Mu-sen
authors.initials: MS
authors.lastname: Ji
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. Seu_dustin82@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. caiyan1980117@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. doctorliujing312@sohu.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. feng102220@126.com.
authors.forename: Hong-feng
authors.initials: HF
authors.lastname: Yang
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. yzliyong0304@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. jinzc57@163.com.
authors.forename: Zhao-chen
authors.initials: ZC
authors.lastname: Jin
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China. jxuzh135@163.com.
authors.forename: Jin-Xu
authors.initials: JX
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008168:Lung / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines