Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome.
Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome.
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干扰素刺激的基因表达的极端与急性呼吸遇险综合征的结局较差。
DOI：
10.1371/journal.pone.0162490
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Malcolm KC
中科院分区：
文献类型：
--
作者：
Nick JA;Caceres SM;Kret JE;Poch KR;Strand M;Faino AV;Nichols DP;Saavedra MT;Taylor-Cousar JL;Geraci MW;Burnham EL;Fessler MB;Suratt BT;Abraham E;Moss M;Malcolm KC
急性呼吸窘迫综合征 (ARDS) 的严重程度可能受到中性粒细胞激活异质性的影响。干扰素刺激基因 (ISG) 是由 I 型干扰素诱导的广泛基因家族，通常作为对病毒感染的反应，引起广泛的免疫调节。我们检验了这样的假设：中性粒细胞免疫调节 ISG 的过度或不足表达与 ARDS 患者较差的临床结果相关。从脓毒症诱导的 ARDS 患者 (n = 31) 和健康对照 (n = 19) 中分离出的循环中性粒细胞的全基因组转录谱用于表征 ISG 表达。表达的层次聚类确定了 3 个具有低、中和高 ISG 表达的不同主题组。确定了表达差异最大的 ISG（MX1、IFIT1 和 ISG15），并用于分析科罗拉多 ARDS 网络站点的前瞻性队列。来自四家城市医院的 120 名 ARDS 患者在开始机械通气后 72 小时内入组。从患者体内分离出循环中性粒细胞，并通过 PCR 测定 ISG 的表达。样本按照与平均值的标准差分为高 (n = 21)、中 (n = 82) 或低 (n = 17) ISG 表达。对 ISG 高或低表达患者与中等表达患者的临床结果进行了比较。入组时，各组之间的年龄、性别、共存医疗状况或生理损伤类型没有差异。调整年龄、种族、性别和 BMI 后，高或低 ISG 表达患者的 28 天无呼吸机和 ICU 天数（P = 0.0006 和 0.0004）以及 90 天死亡率和 90 天在家无辅助呼吸天数（P = 0.02 和 0.004）的临床结果明显较差。这些发现表明，ARDS 患者早期恢复的循环中性粒细胞 ISG 表达极端，与较差的临床结果相关。
Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced by Type I interferons, often as a response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression of immunomodulatory ISG by neutrophils is associated with worse clinical outcomes in patients with ARDS. Genome-wide transcriptional profiles of circulating neutrophils isolated from patients with sepsis-induced ARDS (n = 31) and healthy controls (n = 19) were used to characterize ISG expression. Hierarchical clustering of expression identified 3 distinct subject groups with Low, Mid and High ISG expression. ISG accounting for the greatest variability in expression were identified (MX1, IFIT1, and ISG15) and used to analyze a prospective cohort at the Colorado ARDS Network site. One hundred twenty ARDS patients from four urban hospitals were enrolled within 72 hours of initiation of mechanical ventilation. Circulating neutrophils were isolated from patients and expression of ISG determined by PCR. Samples were stratified by standard deviation from the mean into High (n = 21), Mid, (n = 82) or Low (n = 17) ISG expression. Clinical outcomes were compared between patients with High or Low ISG expression to those with Mid-range expression. At enrollment, there were no differences in age, gender, co-existing medical conditions, or type of physiologic injury between cohorts. After adjusting for age, race, gender and BMI, patients with either High or Low ISG expression had significantly worse clinical outcomes than those in the Mid for number of 28-day ventilator- and ICU-free days (P = 0.0006 and 0.0004), as well as 90-day mortality and 90-day home with unassisted breathing (P = 0.02 and 0.004). These findings suggest extremes of ISG expression by circulating neutrophils from ARDS patients recovered early in the syndrome are associated with poorer clinical outcomes.
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DOI：
10.1016/s1473-3099(06)70466-2
发表时间：
2006-05
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Brundage JF
通讯作者：
Brundage JF
影响因子：
5.4
作者：
Brukman, Alla;Enquist, L. W.
通讯作者：
Enquist, L. W.
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E
影响因子：
3.9
作者：
Bode, Johannes G.;Brenndoerfer, Erwin D.;Haeussinger, Dieter
通讯作者：
Haeussinger, Dieter
影响因子：
3.6
作者：
Halminen, M;Ilonen, J;Makela, MJ
通讯作者：
Makela, MJ