University Division of Anaesthesia, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Box 93, Hills Road, Cambridge, CB2 0QQ, England, UK.
MRC Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh, Scotland, UK.
Intensive Care Med. 2018 May;44(5):627-635. doi: 10.1007/s00134-018-5247-0. Epub 2018 Jun 7.
Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.
Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (T)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.
A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of T were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.
This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.
The study was registered with clinicaltrials.gov (NCT02186522).
细胞免疫功能障碍在重症监护患者中很常见，可预测多种严重并发症。为了进行有效的靶向治疗，需要开发临床适用的方法来检测功能障碍。本研究旨在证实与免疫功能障碍相关的细胞标志物能够对重症患者继发感染的风险进行分层。
对英国 4 家重症监护病房的重症患者进行多中心前瞻性观察队列研究。连续采集血样，使用标准化的流式细胞术对三种与免疫细胞功能障碍相关的细胞表面标志物[中性粒细胞 CD88、单核细胞人类白细胞抗原-DR（HLA-DR）和调节性 T 细胞（T）的比例]进行现场检测。对患者进行随访以观察继发感染的发生情况。
共纳入 148 例患者，其中 138 例可提供数据。中性粒细胞 CD88 减少、单核细胞 HLA-DR 减少和 T 细胞比例升高均与随后感染的发生相关，优势比（95%CI）分别为 2.18（1.00-4.74）、3.44（1.58-7.47）和 2.41（1.14-5.11）。免疫功能障碍的负担预示着感染风险的逐渐增加，从无功能障碍患者的 14%增加至三种标志物均有功能障碍患者的 59%。这些检测方法在入住 ICU 后不久无法对患者进行风险分层，但在第 3 天至第 9 天之间是有效的。
本研究证实了我们之前的发现，即三种细胞表面标志物可预测继发感染的风险，证明了标准化多站点流式细胞术的可行性，并提供了一种可用于靶向未来免疫调节治疗的工具。
该研究在 clinicaltrials.gov 上注册（NCT02186522）。
