Third Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
J Rheumatol. 2011 Feb;38(2):310-6. doi: 10.3899/jrheum.100486. Epub 2010 Nov 15.
DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were performed to identify key target genes in peripheral blood from patients with Sjögren's syndrome (SS).
DNA microarray analysis was performed in 19 patients with SS (all women) and 10 healthy controls (5 men and 5 women) using a low-density DNA microarray system with 778 genes. For confirmation, the expression of upregulated genes was analyzed by quantitative real-time PCR in another 37 SS patients (35 women and 2 men) and 9 healthy controls (8 women and 1 man). Relationships between gene signatures and various clinical measures, such as disease duration, symptoms and signs, complications, immunological findings, and salivary and lacrimal functions, were analyzed.
Interferon-α (IFN-α)-inducible protein 27 (IFI27) showed the most significant difference between SS patients and controls in the microarray screening. We performed quantitative RT-PCR for IFI27. IFI27 gene expression level was increased in patients with SS compared with controls (p < 0.01) by real-time PCR, supporting our observations from the microarray data. The level of IFI27 was significantly correlated with serum IgG levels (r = 0.462, p < 0.01) and ß(2)-microglobulin (r = 0.385, p < 0.05), soluble interleukin 2 receptor (r = 0.473, p < 0.01), erythrocyte sedimentation rate (r = 0.333, p < 0.05), and antinuclear antibody titer (speckled pattern; r = 0.445, p < 0.01).
Our results suggest that upregulation of IFN-inducible genes in SS patients is a systemic phenomenon, and IFN may play an important role in the pathogenesis of SS. The expression level of IFI27 could be an effective and specific biomarker associated with SS.
通过 DNA 微阵列分析和实时定量聚合酶链反应（PCR），鉴定干燥综合征（SS）患者外周血中的关键靶基因。
使用包含 778 个基因的低密度 DNA 微阵列系统，对 19 例 SS 患者（均为女性）和 10 例健康对照者（5 男 5 女）进行 DNA 微阵列分析。为了验证，在另 37 例 SS 患者（35 女 2 男）和 9 例健康对照者（8 女 1 男）中，通过实时定量 PCR 分析上调基因的表达。分析基因特征与各种临床指标（如疾病持续时间、症状和体征、并发症、免疫发现以及唾液和泪液功能）之间的关系。
在微阵列筛选中，干扰素-α（IFN-α）诱导蛋白 27（IFI27）在 SS 患者与对照组之间的差异最显著。我们对 IFI27 进行了定量 RT-PCR。与对照组相比，SS 患者的 IFI27 基因表达水平升高（p<0.01），这支持了我们从微阵列数据中观察到的结果。IFI27 水平与血清 IgG 水平（r=0.462，p<0.01）和β2-微球蛋白（r=0.385，p<0.05）、可溶性白细胞介素 2 受体（r=0.473，p<0.01）、红细胞沉降率（r=0.333，p<0.05）和抗核抗体滴度（斑点型；r=0.445，p<0.01）显著相关。
我们的结果表明，SS 患者中 IFN 诱导基因的上调是一种全身性现象，IFN 可能在 SS 的发病机制中发挥重要作用。IFI27 的表达水平可能是与 SS 相关的有效且特异的生物标志物。
