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鉴定干扰素诱导基因作为系统性红斑狼疮的诊断生物标志物。

Identification of interferon-inducible genes as diagnostic biomarker for systemic lupus erythematosus.

作者信息

Feng Xuebing, Huang Jing, Liu Yan, Xiao Lihui, Wang Dandan, Hua Bingzhu, Tsao Betty P, Sun Lingyun

机构信息

Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China,

出版信息

Clin Rheumatol. 2015 Jan;34(1):71-9. doi: 10.1007/s10067-014-2799-4. Epub 2014 Oct 26.

Abstract

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.

摘要

生物标志物的鉴定有助于进行早期诊断,从而有益于系统性红斑狼疮(SLE)患者的预后,其中延迟治疗已被认为是一个独立的不良预后因素。在本研究中,我们评估了五种I型干扰素(IFN)诱导基因(LY6E、OAS1、OASL、MX1和ISG15)的表达水平及总IFN评分对SLE的诊断价值。应用定量实时PCR测定69例SLE患者、42例其他结缔组织病患者和26例正常对照外周血转录水平的基因表达。与正常受试者和疾病对照相比,SLE患者中五个基因的表达及根据IFN诱导基因表达计算出的IFN评分均显著升高。IFN评分与年龄、性别和类固醇剂量无关,但与SLE疾病活动指数呈弱相关。SLE患者中基因表达均与合并感染状态或抗EB病毒抗体升高无关。改良IFN评分(由三个主要IFN诱导基因的表达计算得出)和LY6E水平在区分SLE患者与疾病对照以及正常受试者方面均显示出良好的诊断准确性(受试者操作特征曲线下面积分别为0.812和0.815),在截断值为2.37和3.23时,特异性为70 - 80%,敏感性为70 - 80%。总之,IFN诱导基因高表达是SLE患者的特征。单独的改良IFN评分或LY6E水平可作为SLE诊断的良好生物标志物。

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