Could 2′5′-oligoadenylate synthetase isoforms be biomarkers to differentiate between disease flare and infection in lupus patients? A pilot study

Could 2′5′-oligoadenylate synthetase isoforms be biomarkers to differentiate between disease flare and infection in lupus patients? A pilot study
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DOI:
10.1007/s10067-006-0260-z
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发表时间:
2006-03
影响因子:
3.4
通讯作者:
S. Ye;Qiang Guo;Jian-ping Tang;Cheng-de Yang;N. Shen;Shun‐le Chen
S. Ye;Qiang Guo;Jian-ping Tang;Cheng-de Yang;N. Shen;Shun‐le Chen
中科院分区:
医学3区
文献类型:
--
作者:
S. Ye;Qiang Guo;Jian-ping Tang;Cheng-de Yang;N. Shen;Shun‐le Chen

文献摘要

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2‘5’-寡腺苷合成酶(OAS)早在20年前就被发现与系统性红斑狼疮(SLE)有关,最近几个微阵列的基因表达研究又发现OAS参与了SLE的I型干扰素途径。本研究的目的是研究OAS亚型在狼疮患者中的表达,评估它们是否可以成为区分疾病发作和感染的生物标志物。54名以发热或全身性炎症综合征或两者兼有的SLE患者入选。采用实时荧光定量聚合酶链式反应技术检测29例活动期系统性红斑狼疮(SLEDAI≥9,n=29)和25例合并感染的SLE患者OAS1、OAS2和OASL基因的表达。后者由19例侵袭性细菌感染患者和6例病毒感染患者组成。同时检测C反应蛋白(CRP)等临床指标。29名健康人组成正常对照组。狼疮活动期患者OAS1、OAS2和OASLmRNA的表达均高于感染组(P<0.05)和正常对照组(P<0.001)。系统性红斑狼疮合并感染患者的OAS1表达水平较正常对照组高(P=0.002),OASL表达水平较低(P=0.004),OAS2表达水平与正常对照组相当(P=0.135)。Logistic回归分析显示,OASL表达水平与狼疮感染呈负相关(p=0.008)。预测感染的受试者工作特征曲线下面积OASL为0.92(p&lt;0.0001),CRP为0.77(p=0.007)。因此,我们的初步数据表明,OAS亚型的表达模式,特别是OASL,可能为鉴别SLE的疾病红斑和某些感染提供有用的信息。
2′5′-Oligoadenylate synthetase (OAS) was shown to be related to systemic lupus erythematosus (SLE) 20 years ago, and was rediscovered to be involved in type I interferon pathway in SLE by several microarray gene expression studies recently. The goal of this study was to investigate OAS isoform expressions in lupus patients, to evaluate whether they could become biomarkers to differentiate between disease flare and infection. Fifty-four SLE patients presented with fever or systemic inflammatory syndrome, or both, were enrolled. Gene expressions of OAS1, OAS2, and OASL were studied by using real time PCR in active SLE (SLEDAI ≥9,n=29) and in those complicated with infections (n=25). The latter group was composed of 19 patients with invasive bacterial infections, and six patients with viral infections. C reactive protein (CRP) and other clinical parameters were also measured. Twenty-nine healthy individuals made up a normal control group. The mRNA expressions of OAS1, OAS2, and OASL were higher in patients with lupus flares than those with infections (p<0.03), or normal controls (p<0.001). SLE complicated with infections have higher OAS1 expression level (P=0.002), lower OASL (P=0.004), and equivalent OAS2 (P=0.135), when compared with those of normal controls. OASL expression level was negatively correlated with infection in lupus by logistic regression analysis (p=0.008). Area under the receiver operating characteristic curve for the prediction of infection was 0.92 (p<0.0001) for OASL, and 0.77 (p=0.007) for CRP. Therefore, our preliminary data suggest that the pattern of OAS isoform expressions, OASL in particular, may provide useful information in differentiating disease flares from certain infections in SLE.