Interferon signature gene expression is correlated with autoantibody profiles in patients with incomplete lupus syndromes
Interferon signature gene expression is correlated with autoantibody profiles in patients with incomplete lupus syndromes
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DOI：
10.1111/j.1365-2249.2009.04057.x
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发表时间：
2010-03-01
影响因子：
4.6
通讯作者：
Olsen, N. J.
中科院分区：
文献类型：
--
作者：
Li, Q. -Z.;Zhou, J.;Olsen, N. J.
干扰素（IFN）标签基因已被证明在系统性红斑狼疮（SLE）患者的外周血中高度表达，特别是在存在活动性疾病的情况下。然而，该基因签名在具有不完全形式的狼疮的个体中的表达以及IFN签名基因与自身抗体产生之间的致病关系尚未被充分探索。在本研究中，我们检查了诊断为不完全性红斑狼疮（ILE）的患者的基因表达和自身抗体谱，以确定基因表达特征与自身抗体产生的相关性。使用来自84名受试者的血液样品在24 K Illumina Human Refseq-8阵列上进行基因表达分析，所述受试者包括患有SLE（n = 27）或ILE（n = 24）的患者、这些患者的一级亲属（FDR）（n = 22）和非自身免疫对照（NC）个体（n = 11）。使用标准免疫测定和自身抗原蛋白质组学阵列测量自身抗体表达。在83%的SLE患者和50%的ILE患者中观察到一组63个IFN标签基因的上调。ILE和SLE中IFN基因的高水平表达与IgG自身抗体亚群的表达显著相关，包括染色质、dsDNA、dsRNA、U1 snRNP、Ro/SSA、La/SSB、拓扑异构酶I和Scl 70，而低水平的IFN水平与免疫球蛋白（IG）M自身反应性相关。这些研究表明，在ILE患者中，IFN基因表达特征可以识别出这些个体中有疾病进展风险的一个子集。此外，高水平的α IFN可能促进自身抗体从IgM类转换为更具致病性的IgG类。
Interferon (IFN) signature genes have been shown to be expressed highly in peripheral blood of patients with systemic lupus erythematosus (SLE), especially in the presence of active disease. However, the expression of this gene signature in individuals with incomplete forms of lupus and the pathogenic relationship between IFN signature genes and autoantibody production have not been explored fully. In the present study, we examined the gene expression and autoantibody profiles of patients diagnosed with incomplete lupus erythematosus (ILE) to determine correlations of the gene expression signature with autoantibody production. Gene expression analysis was carried out on the 24K Illumina Human Refseq-8 arrays using blood samples from 84 subjects, including patients with SLE (n = 27) or ILE (n = 24), first-degree relatives (FDR) of these patients (n = 22) and non-autoimmune control (NC) individuals (n = 11). Autoantibody expression was measured using standard immunoassays and autoantigen proteomic arrays. Up-regulation of a set of 63 IFN signature genes was seen in 83% of SLE patients and 50% of ILE patients. High levels of IFN gene expression in ILE and SLE showed significant correlations with the expression of a subset of IgG autoantibodies, including chromatin, dsDNA, dsRNA, U1snRNP, Ro/SSA, La/SSB, topoisomerase I and Scl 70, while low IFN levels were correlated with immunoglobulin (Ig)M autoreactivity. These studies suggest that in patients with ILE the IFN gene expression signature may identify a subset of these individuals who are at risk for disease progression. Furthermore, high levels of alpha IFN may promote autoantibody class-switch from IgM to the more pathogenic IgG class.