Identification of biomarkers of response to IFNg during endotoxin tolerance: application to septic shock.
Identification of biomarkers of response to IFNg during endotoxin tolerance: application to septic shock.
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DOI：
10.1371/journal.pone.0068218
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Monneret G
中科院分区：
文献类型：
--
作者：
Allantaz-Frager F;Turrel-Davin F;Venet F;Monnin C;De Saint Jean A;Barbalat V;Cerrato E;Pachot A;Lepape A;Monneret G
脓毒症患者中显著免疫抑制特征的快速发展与院内感染和死亡率的风险增加相关，这代表了脓毒症免疫靶向治疗的合理性。然而，由于没有免疫功能障碍的临床迹象，目前的挑战是开发生物标志物，帮助临床医生识别将从免疫治疗中受益的患者并监测其疗效。使用内毒素耐受（ET）的体外模型，脓毒症诱导的单核细胞免疫抑制的关键特征，我们通过微阵列基因表达谱鉴定了一组与ET发展相关的转录本，其表达在干扰素-γ（IFN-γ）免疫刺激后恢复。这些结果通过qRT-PCR证实。重要的是，在患者中进一步评估了标记物的短列表。在这些转录物中，在离体LPS刺激后，与健康血液相比，六种（TNFAIP 6、FCN 1、CXCL 10、GBP 1、CXCL 5和PID 1）在脓毒症患者的血液中差异表达，并且通过IFN-γ恢复。在这项研究中，通过将体外模型中的微阵列方法与临床样本中的验证相结合，我们确定了一组六种新的转录本，可用于鉴定符合IFNg治疗条件的脓毒症患者。沿着先前鉴定的标志物TNF α、IL 10和HLA-TNF α，这些标志物的潜在价值现在应该在更大的患者队列中进行评估。在有利的结果下，它们可以作为免疫刺激治疗前的分层工具，并监测药物疗效。
The rapid development in septic patients of features of marked immunosuppression associated with increased risk of nosocomial infections and mortality represents the rational for the initiation of immune targeted treatments in sepsis. However, as there is no clinical sign of immune dysfunctions, the current challenge is to develop biomarkers that will help clinicians identify the patients that would benefit from immunotherapy and monitor its efficacy. Using an in vitro model of endotoxin tolerance (ET), a pivotal feature of sepsis-induced immunosuppression in monocytes, we identified using gene expression profiling by microarray a panel of transcripts associated with the development of ET which expression was restored after immunostimulation with interferon-gamma (IFN-γ). These results were confirmed by qRT-PCR. Importantly, this short-list of markers was further evaluated in patients. Of these transcripts, six (TNFAIP6, FCN1, CXCL10, GBP1, CXCL5 and PID1) were differentially expressed in septic patients’ blood compared to healthy blood upon ex vivo LPS stimulation and were restored by IFN-γ. In this study, by combining a microarray approach in an in vitro model and a validation in clinical samples, we identified a panel of six new transcripts that could be used for the identification of septic patients eligible for IFNg therapy. Along with the previously identified markers TNFa, IL10 and HLA-DRA, the potential value of these markers should now be evaluated in a larger cohort of patients. Upon favorable results, they could serve as stratification tools prior to immunostimulatory treatment and to monitor drug efficacy.
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影响因子：
8.8
作者：
Nakos, G;Malamou-Mitsi, VD;Lekka, ME
通讯作者：
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DOI：
10.1186/cc5055
发表时间：
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期刊：
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影响因子：
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作者：
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作者：
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影响因子：
2.1
作者：
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