Lack of association between the interferon-α signature and longitudinal changes in disease activity in systemic lupus erythematosus
Lack of association between the interferon-α signature and longitudinal changes in disease activity in systemic lupus erythematosus
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DOI：
10.1136/ard.2008.093146
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发表时间：
2009-09-01
影响因子：
27.4
通讯作者：
Wither, J.
中科院分区：
文献类型：
--
作者：
Landolt-Marticorena, C.;Bonventi, G.;Wither, J.
目的：为研究干扰素（IFN）诱导基因在系统性红斑狼疮（SLE）中的纵向表达，探讨其作为疾病生物标志物的可行性，从94例SLE患者和11例对照外周血中提取RNA，逆转录成cDNA。通过定量PCR测定五种IFN应答基因（LY 6 E、OAS 1、IFIT 1、ISG 15和MX 1）的表达水平，标准化为GAPDH并求和以产生总体IFN评分。患者进行了纵向随访，为期312个月，和疾病活动之间的关联，测量的SLE疾病活动指数（SLEDAI-2K），和其他临床和实验室变量examined.Results：所有5个IFN-应答基因的表达显着高于SLE患者比对照组。LY 6 E、OAS 1、IFIT 1的表达和总体IFN评分与高疾病活动性相关。总体IFN评分也与活动性肾脏疾病、C3降低以及单个时间点存在抗dsDNA或抗RNA结合蛋白抗体相关。然而，有一个穷人之间的相关性，在这个分数的变化和疾病活动的变化，C3或抗dsDNA抗体水平的患者纵向。在大多数患者中，IFN诱导的基因表达水平在3-12个月内保持相对稳定，尽管疾病活动有显著变化。然而，在低/中度疾病活动的患者中，那些具有高IFN分数有一个更近期的历史，持续的高疾病activity.Conclusion：研究结果表明，IFN诱导的基因表达作为疾病活动的急性变化的生物标志物具有有限的临床实用性。
Objective: To study the longitudinal expression of interferon (IFN)-inducible genes in systemic lupus erythematosus (SLE) and determine their suitability as disease biomarkers.Methods: RNA was isolated from the peripheral blood of 94 patients with SLE and 11 controls and reverse transcribed into cDNA. The expression levels of five IFN-responsive genes (LY6E, OAS1, IFIT1, ISG15 and MX1) were determined by quantitative PCR, normalised to GAPDH and summed to generate a global IFN score. Patients were followed longitudinally for a period of 312 months, and the association between disease activity, as measured by the SLE disease activity index (SLEDAI-2K), and other clinical and laboratory variables was examined.Results: The expression of all five IFN-responsive genes was significantly higher in patients with SLE than in controls. The expression of LY6E, OAS1, IFIT1 and the global IFN score was associated with high disease activity. The global IFN score was also associated with active renal disease, a decreased C3, and the presence of anti-dsDNA or anti-RNA binding protein antibodies at a single point in time. However, there was a poor correlation between changes in this score and changes in disease activity, C3 or anti-dsDNA antibody levels in patients followed longitudinally. In most patients the levels of IFN-induced gene expression remained relatively stable over 3-12 months despite marked changes in disease activity. Nevertheless, in patients with low/moderate disease activity, those with high IFN scores had a more recent history of sustained high disease activity.Conclusion: The findings indicate that IFN-induced gene expression has limited clinical utility as a biomarker of acute changes in disease activity.