Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon in dermatomyositis
Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon in dermatomyositis
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DOI：
10.1111/bjd.15006
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发表时间：
2017-05-01
影响因子：
10.3
通讯作者：
Greenberg, S. A.
中科院分区：
文献类型：
--
作者：
Huard, C.;Gulla, S. V.;Greenberg, S. A.
背景皮肌炎（DM）是一种主要累及皮肤和肌肉的自身免疫性疾病，本研究的目的是确定DM患者临床皮肤病活动性（采用经验证的皮肤皮肌炎疾病面积和严重程度指数（CDASI）测量）与血液中1型干扰素（IFN）通路生物标志物之间是否存在关联。前瞻性地招募了2名患有DM的患者和25名健康志愿者。获得CDASI评分，并从所有参与者中分离血清和血液RNA。CDASI活性和1型IFN-诱导的基因签名之间的关联进行了评估，在所有患者样本的横截面和纵向上13对访问通过transformational profiling analysis.ResultsBy RNAseq分析，1型IFN-诱导的基因是最高度差异调节。CDASI活性阈值为12与升高的1型IFN基因特征和血清IFN-相关，但与IFN-蛋白无关。表达分析显示，所有轻度疾病活动的患者具有低的1型IFN基因签名，而93%的中度至高度疾病活动的患者具有升高的基因签名。在纵向分析中，CDASI活性的变化表现出非显着的趋势与一致的方向性变化的基因significant.ConclusionsA型1 IFN途径签名生物标志物在血液中是高度相关的CDASI活性评分在DM，可能是一个有前途的替代临床试验终点。血清IFN-γ而非IFN-γ与基因特征和CDASI的相关性表明IFN-γ驱动DM的疾病活动。
BackgroundDermatomyositis (DM) is an autoimmune disease primarily affecting skin and muscle.ObjectivesThe purpose of this study was to determine whether an association exists between clinical skin disease activity as measured by the validated Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and type 1 interferon (IFN) pathway biomarkers in the blood of patients with DM.MethodsForty-two patients with DM and 25 healthy volunteers were prospectively enrolled. CDASI scores were obtained, and serum and blood RNA were isolated from all participants. Associations between CDASI activity and type 1 IFN-inducible gene signature were assessed cross-sectionally in all patient samples and longitudinally on 13 paired visits via transcriptional profiling analyses.ResultsBy RNAseq analysis, type 1 IFN-inducible genes were the most highly differentially regulated. A CDASI activity threshold of 12 was correlated with an elevated type 1 IFN gene signature and with serum IFN-, but not with IFN- protein. Expression analysis showed that all patients with mild disease activity had a low type 1 IFN gene signature, while 93% of patients with moderate-to-high disease activity had elevated gene signature. In longitudinal analysis, changes in CDASI activity showed nonsignificant trends with concordant directional changes in gene signature.ConclusionsA type 1 IFN pathway signature biomarker in blood is highly correlated with CDASI activity scores in DM, and may be a promising surrogate clinical trial end point. The correlation of serum IFN-, but not IFN-, with both a gene signature and CDASI suggests that IFN- drives disease activity in DM.