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严重多发伤患者免疫抑制基因表达生物标志物与输血的相关性。

Association between gene expression biomarkers of immunosuppression and blood transfusion in severely injured polytrauma patients.

机构信息

*Adult Critical Care Unit, Royal London Hospital, Barts Health NHS Trust, London †Centre for Trauma Sciences, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London ‡Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London §Genome Centre, John Vane Science Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, United Kingdom.

出版信息

Ann Surg. 2015 Apr;261(4):751-9. doi: 10.1097/SLA.0000000000000653.

Abstract

OBJECTIVE

To explore the hypothesis that blood transfusion contributes to an immunosuppressed phenotype in severely injured patients.

BACKGROUND

Despite trauma patients using disproportionately large quantities of blood and blood products, the immunomodulatory effects of blood transfusion in this group are inadequately described.

METHODS

A total of 112 ventilated polytrauma patients were recruited. Messenger RNA (mRNA) was extracted from PAXGene tubes collected within 2 hours of the trauma, at 24 hours, and at 72 hours. T-helper cell subtype specific cytokines and transcription factors were quantified using real-time polymerase chain reaction.

RESULTS

Median injury severity score was 29. Blood transfusion was administered to 27 (24%) patients before the 2-hour sampling point. Transfusion was associated with a greater immediate rise in IL-10 (P = 0.003) and IL-27 (P = 0.04) mRNA levels. Blood products were transfused in 72 (64%) patients within the first 24 hours. There was an association between transfusion at 24 hours and higher IL-10 (P < 0.0001), lower Foxp3 (P = 0.01), GATA3 (P = 0.006), and RORγt (P = 0.05) mRNA levels at 24 hours. There were greater reductions in T-bet (P = 0.03) mRNA levels and lesser increases in TNFα (P = 0.015) and IFNγ (P = 0.035) at 24 hours in those transfused. Multiple regression models confirmed that the transfusion of blood products was independently associated with altered patterns of gene expression. Blood stream infections occur in 15 (20.8%) of those transfused in the first 24 hours, compared with 1 patient (2.5%) not transfused (OR = 10.3 [1.3-81], P = 0.008).

CONCLUSIONS

The primarily immunosuppressive inflammatory response to polytrauma may be exacerbated by the transfusion of blood products. Furthermore, transfusion was associated with an increased susceptibility to nosocomial infections.

摘要

目的

探讨输血导致严重创伤患者出现免疫抑制表型的假说。

背景

尽管创伤患者使用了不成比例的大量血液和血液制品,但输血对该人群的免疫调节作用描述不足。

方法

共纳入 112 例接受机械通气的多发伤患者。在创伤后 2 小时内、24 小时和 72 小时内从 PAXGene 管中提取信使 RNA(mRNA)。使用实时聚合酶链反应定量测定 T 辅助细胞亚群特异性细胞因子和转录因子。

结果

中位创伤严重程度评分 29 分。27 例(24%)患者在 2 小时采样点前接受输血。输血与立即升高的白细胞介素 10(IL-10)(P=0.003)和白细胞介素 27(IL-27)(P=0.04)mRNA 水平相关。72 例(64%)患者在 24 小时内输注血液制品。24 小时输血与更高的 IL-10(P<0.0001)、更低的 Foxp3(P=0.01)、GATA3(P=0.006)和 RORγt(P=0.05)mRNA 水平相关。在输血患者中,T 细胞激活蛋白(T-bet)(P=0.03)mRNA 水平下降更大,肿瘤坏死因子-α(TNF-α)(P=0.015)和干扰素-γ(IFN-γ)(P=0.035)增加更少。多变量回归模型证实,血液制品的输血与基因表达模式的改变独立相关。与未输血的 1 例患者(2.5%)相比,在 24 小时内输血的 15 例患者(20.8%)发生血流感染(OR=10.3[1.3-81],P=0.008)。

结论

多发伤的主要抗炎反应可能因血液制品的输血而加剧。此外,输血与医院获得性感染的易感性增加有关。

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