Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease.
Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease.
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DOI：
10.1007/s10875-016-0359-1
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发表时间：
2017-02
影响因子：
9.1
通讯作者：
Crow YJ
中科院分区：
文献类型：
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作者：
Rice GI;Melki I;Frémond ML;Briggs TA;Rodero MP;Kitabayashi N;Oojageer A;Bader-Meunier B;Belot A;Bodemer C;Quartier P;Crow YJ
I型干扰素的增加被认为与一些单基因和复杂疾病的病理有关，这些疾病横跨儿童风湿病、神经病学和皮肤病。然而，在常规的临床实践中，没有测试来识别增强的干扰素信号，从而限制了对这些疾病的诊断和监测治疗的能力。在这里，我们开始研究一种检测一组干扰素刺激基因(ISGs)在受一系列炎症性疾病影响的儿童中表达的方法的使用。2011年至2016年，英国曼彻斯特大学和法国巴黎想象研究所进行了一项队列研究。RNA PAX基因血液样本和临床数据来自对照组和具有遗传确认或临床明确炎症表型的有症状的患者。通过定量聚合酶链式反应测量6个ISGs的表达，并使用中位数折叠变化来计算每个受试者的干扰素得分(IS)，与先前由29名对照组成的小组进行比较(其中对照数据的+2 SD，IS=2.466被认为是异常的)。结果与遗传和临床数据相关联。对992份样本进行了分析，其中包括24种炎症基因/表型的有症状患者、未受影响的杂合子携带者和对照组。与对照组(78例，65例；中位数为0.688，IQR 0.427-1.196)、青少年系统性红斑狼疮(78例，55例，IQR3.99-17.27)和青少年皮肌炎(101例，59例；中位数为9.02，IQR2.51-21.73)相比，13例单基因疾病(455例，265例；中位数为10.73，四分位数范围为5.90-18.41)、青少年系统性红斑狼疮(78例，55例；中位数为10.60，IQR3.99-17.27)、杂合子突变携带者(89例，76例；中位数为0.862，IQR为0.493-1.942)，以及非分子定义的自身炎症患者(89例，69名患者；中位数为1.07，IQR为0.491-3.74)。对6个ISG的评估可以用来定义与增强的I型干扰素信号有关的一系列炎症性疾病。如果未来的研究表明IS是一种反应性生物标记物，这一措施可能会被证明在诊断和评估治疗效果方面都很有用。本文的在线版本(doi：10.1007/s10875-0160359-1)包含补充材料，授权用户可以使用。
Increased type I interferon is considered relevant to the pathology of a number of monogenic and complex disorders spanning pediatric rheumatology, neurology, and dermatology. However, no test exists in routine clinical practice to identify enhanced interferon signaling, thus limiting the ability to diagnose and monitor treatment of these diseases. Here, we set out to investigate the use of an assay measuring the expression of a panel of interferon-stimulated genes (ISGs) in children affected by a range of inflammatory diseases. A cohort study was conducted between 2011 and 2016 at the University of Manchester, UK, and the Institut Imagine, Paris, France. RNA PAXgene blood samples and clinical data were collected from controls and symptomatic patients with a genetically confirmed or clinically well-defined inflammatory phenotype. The expression of six ISGs was measured by quantitative polymerase chain reaction, and the median fold change was used to calculate an interferon score (IS) for each subject compared to a previously derived panel of 29 controls (where +2 SD of the control data, an IS of >2.466, is considered as abnormal). Results were correlated with genetic and clinical data. Nine hundred ninety-two samples were analyzed from 630 individuals comprising symptomatic patients across 24 inflammatory genotypes/phenotypes, unaffected heterozygous carriers, and controls. A consistent upregulation of ISG expression was seen in 13 monogenic conditions (455 samples, 265 patients; median IS 10.73, interquartile range (IQR) 5.90–18.41), juvenile systemic lupus erythematosus (78 samples, 55 patients; median IS 10.60, IQR 3.99–17.27), and juvenile dermatomyositis (101 samples, 59 patients; median IS 9.02, IQR 2.51–21.73) compared to controls (78 samples, 65 subjects; median IS 0.688, IQR 0.427–1.196), heterozygous mutation carriers (89 samples, 76 subjects; median IS 0.862, IQR 0.493–1.942), and individuals with non-molecularly defined autoinflammation (89 samples, 69 patients; median IS 1.07, IQR 0.491–3.74). An assessment of six ISGs can be used to define a spectrum of inflammatory diseases related to enhanced type I interferon signaling. If future studies demonstrate that the IS is a reactive biomarker, this measure may prove useful both in the diagnosis and the assessment of treatment efficacy. The online version of this article (doi:10.1007/s10875-016-0359-1) contains supplementary material, which is available to authorized users.