Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE.
Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE.
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DOI：
10.1136/lupus-2014-000080
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发表时间：
2015
影响因子：
3.9
通讯作者：
Townsend MJ
中科院分区：
文献类型：
--
作者：
Kennedy WP;Maciuca R;Wolslegel K;Tew W;Abbas AR;Chaivorapol C;Morimoto A;McBride JM;Brunetta P;Richardson BC;Davis JC Jr;Behrens TW;Townsend MJ
系统性红斑狼疮（SLE）患者的干扰素（IFN）信号（IS）包括超过100个由I型IFN通路激活诱导的基因。我们开发了一种使用三个基因来量化IS的方法- IS度量(ISM) -并从多个临床试验中描述了具有不同ISM状态的SLE患者的临床特征。来自SLE患者训练队列的血液微阵列表达数据证实了IS的存在，并确定了替代基因。我们用定量PCR （qPCR）检测这些基因，从IS中得到一个ISM。从四项临床试验中评估肾外狼疮和狼疮性肾炎患者ISM状态与临床疾病特征的关系。HERC5、EPSTI和CMPK2三个基因与IS相关性良好（p>0.96），组成ISM qPCR检测。使用健康对照数据的第95百分位，来自不同研究的SLE患者被分为ISM低和ISM高两个亚组，这些亚组在36周内纵向稳定。ISM-High状态与高滴度的抗dsdna抗体、抗可提取核抗原自身抗体、血清肿瘤坏死因子家族B细胞活化因子（BAFF）水平升高和低补体血症之间存在显著关联。然而，ism高组和ism低组的总体临床疾病活动性测量是相似的。ISM是一种is生物标志物，可将SLE患者分为两个亚群——ISM高亚群和ISM低亚群，具有不同的血清学表现。ISM不能区分疾病活动性的高低，但在识别更有可能对靶向IFN-α治疗有反应的患者时可能有用。NCT00962832。
The interferon (IFN) signature (IS) in patients with systemic lupus erythematosus (SLE) includes over 100 genes induced by type I IFN pathway activation. We developed a method to quantify the IS using three genes—the IS metric (ISM)—and characterised the clinical characteristics of patients with SLE with different ISM status from multiple clinical trials. Blood microarray expression data from a training cohort of patients with SLE confirmed the presence of the IS and identified surrogate genes. We assayed these genes in a quantitative PCR (qPCR) assay, yielding an ISM from the IS. The association of ISM status with clinical disease characteristics was assessed in patients with extrarenal lupus and lupus nephritis from four clinical trials. Three genes, HERC5, EPSTI and CMPK2, correlated well with the IS (p>0.96), and composed the ISM qPCR assay. Using the 95th centile for healthy control data, patients with SLE from different studies were classified into two ISM subsets—ISM-Low and ISM-High—that are longitudinally stable over 36 weeks. Significant associations were identified between ISM-High status and higher titres of anti-dsDNA antibodies, presence of anti extractable nuclear antigen autoantibodies, elevated serum B cell activating factor of the tumour necrosis factor family (BAFF) levels, and hypocomplementaemia. However, measures of overall clinical disease activity were similar for ISM-High and ISM-Low groups. The ISM is an IS biomarker that divides patients with SLE into two subpopulations—ISM-High and ISM-Low—with differing serological manifestations. The ISM does not distinguish between high and low disease activity, but may have utility in identifying patients more likely to respond to treatment(s) targeting IFN-α. NCT00962832.