Identification of interferon-inducible genes as diagnostic biomarker for systemic lupus erythematosus
Identification of interferon-inducible genes as diagnostic biomarker for systemic lupus erythematosus
复制标题
干扰素诱导基因作为系统性红斑狼疮诊断生物标志物的鉴定
DOI：
10.1007/s10067-014-2799-4
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发表时间：
2015-01-01
影响因子：
3.4
通讯作者：
Sun, Lingyun
中科院分区：
文献类型：
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作者：
Feng, Xuebing;Huang, Jing;Sun, Lingyun
系统性红斑狼疮（systemic lupus erythematosus，SLE）患者治疗延迟是其独立的不良预后因素，生物标志物的识别有助于早期诊断，从而改善患者的预后。在这项研究中，我们评估了5个I型干扰素（IFN）诱导基因（LY 6 E，OAS 1，OASL，MX 1和ISG 15）的表达水平和总IFN评分对SLE的诊断价值。应用实时荧光定量PCR技术检测69例SLE患者、42例其他结缔组织病患者和26例正常对照者外周血基因转录水平的表达。与正常人和疾病对照组相比，SLE患者的5个基因表达和根据IFN诱导基因表达计算的IFN评分均显著增加。IFN评分与年龄、性别和类固醇剂量无关，但与SLE疾病活动指数弱相关。这些基因表达与SLE患者的合并感染状态或EB病毒抗体升高无关。改良IFN评分结果表明，SLE患者血清中IFN-γ、IFN-γ（受试者工作特征曲线下面积分别为0.812和0.815），在2.37和3.23的截止值处具有70- 80%的特异性和70- 80%的灵敏度。总之，高IFN诱导基因表达是SLE患者的体质。改良IFN评分或LY 6 E水平单独作为SLE诊断的良好生物标志物。
The identification of biomarkers helps to perform early diagnosis, thus benefits the outcome of patients with systemic lupus erythematosus (SLE), in which delayed treatment has been proposed as an independent adverse prognostic factor. In this study, we assessed the values of expression levels of five type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) and total IFN score for the diagnosis of SLE. Quantitative real-time PCR was applied to determine gene expressions at transcription level in peripheral blood from 69 SLE patients, 42 patients with other connective tissue diseases, and 26 normal controls. Expressions of five genes and IFN score, calculated according to the expressions of IFN-inducible genes, were all significantly increased in SLE patients compared to those in normal subjects and disease controls. IFN score was not related to age, gender, and the dose of steroids, but weakly correlated with SLE disease activity index. None of the gene expression was associated with concomitant infection status or elevated antibodies against Epstein–Barr (EB) virus in SLE. Both modified IFN score (calculated by the expression of three major IFN-inducible genes) and LY6E level showed good diagnostic accuracy in discriminating between SLE patients and disease controls as well as normal subjects (area under the receiver operating characteristic curve was 0.812 and 0.815, respectively), with 70–80 % specificity and 70–80 % sensitivity at the cutoff of 2.37 and 3.23. In conclusion, high IFN-inducible gene expression is constitutional for SLE patients. The modified IFN score or the LY6E level alone may serve as good biomarkers for SLE diagnosis.