Nikpour M, Dempsey A A, Urowitz M B, Gladman D D, Barnes D A
University of Toronto Lupus Clinic and Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada.
Ann Rheum Dis. 2008 Aug;67(8):1069-75. doi: 10.1136/ard.2007.074765. Epub 2007 Dec 6.
To determine whether peripheral blood gene expression of patients with systemic lupus erythaematosus (SLE) correlates with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K).
RNA was isolated from peripheral blood of 269 patients with SLE and profiled on a custom microarray. Hierarchical clustering and a heat map were used to categorise samples into major clusters based on gene expression pattern. Correlates, including demographic and disease-related characteristics such as SLEDAI-2K score, of the major sample clusters were compared using multivariate regression models.
A set of 31 interferon (IFN)-regulated genes were seen to be driving the separations of samples into two clusters, one characterised by a relatively high IFN-regulated gene signature (n = 150) and the other by a relatively low IFN-regulated gene signature (n = 119). Disease activity measured using the SLEDAI-2K was significantly correlated with the high IFN gene signature. In multivariate regression analysis the immunological component of the SLEDAI-2K was a significant correlate of the high IFN gene signature as was presence of antibodies to U1RNP. There were no discernable correlates of the 156 non-IFN regulated genes profiled on the custom array.
Peripheral blood gene expression profiling (GEP) in SLE allows patients to be categorised into two groups based on a high or low IFN gene signature. Disease activity measured using the SLEDAI-2K is correlated with the high IFN gene signature, indicating that GEP may be a useful biomarker of disease activity in SLE.
确定系统性红斑狼疮（SLE）患者的外周血基因表达是否与使用2000年SLE疾病活动指数（SLEDAI - 2K）测量的疾病活动相关。
从269例SLE患者的外周血中分离RNA，并在定制微阵列上进行分析。使用层次聚类和热图根据基因表达模式将样本分类为主要簇。使用多变量回归模型比较主要样本簇的相关因素，包括人口统计学和疾病相关特征，如SLEDAI - 2K评分。
一组31个干扰素（IFN）调节基因被发现驱动样本分为两个簇，一个簇的特征是IFN调节基因特征相对较高（n = 150），另一个簇的特征是IFN调节基因特征相对较低（n = 119）。使用SLEDAI - 2K测量的疾病活动与高IFN基因特征显著相关。在多变量回归分析中，SLEDAI - 2K的免疫成分以及抗U1RNP抗体的存在是高IFN基因特征的显著相关因素。在定制阵列上分析的156个非IFN调节基因没有可识别的相关因素。
SLE患者的外周血基因表达谱分析（GEP）可根据高或低IFN基因特征将患者分为两组。使用SLEDAI - 2K测量的疾病活动与高IFN基因特征相关，表明GEP可能是SLE疾病活动的有用生物标志物。
