Translational Sciences, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
Ann Rheum Dis. 2011 Nov;70(11):2029-36. doi: 10.1136/ard.2011.150326. Epub 2011 Jul 28.
To characterise activation of the type I interferon (IFN) pathway in patients with systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA) and systemic scleroderma (SSc) and to evaluate the potential to develop a molecular diagnostic tool from the peripheral blood that reflects this activation in disease-affected tissues.
Overexpressed transcripts were identified in the whole blood (WB) of 262 patients with SLE, 44 with DM, 33 with PM, 28 with SSc and 89 with RA and compared with 24 healthy subjects using Affymetrix microarrays. A five gene type I IFN signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type I IFN pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the WB with clinical measurements.
A common set of 36 type I IFN inducible transcripts were identified among the most overexpressed in the WB of all subjects. Significant activation of the type I IFN pathway in subgroups of each of the five diseases studied was observed. Baseline disease activity measurements correlated with a type I IFN gene signature in the WB of subjects with SLE, PM and SSc, as did various serum autoantibody levels in subjects with SLE and DM. This signature was also well correlated between disease-affected tissue and WB in subjects with SLE, DM, PM and SSc.
The results indicate that the type I IFN pathway is activated in patient subsets of five rheumatic diseases and suggest that these subsets may benefit from anti-IFN therapy.
描述系统性红斑狼疮（SLE）、皮肌炎（DM）、多发性肌炎（PM）、类风湿关节炎（RA）和系统性硬皮病（SSc）患者 I 型干扰素（IFN）途径的激活情况，并评估从外周血中开发反映疾病组织中这种激活的分子诊断工具的潜力。
使用 Affymetrix 微阵列比较了 262 例 SLE 患者、44 例 DM 患者、33 例 PM 患者、28 例 SSc 患者和 89 例 RA 患者的全血（WB）中的过表达转录本与 24 名健康对照者。在这些患者中评估了五个基因 I 型 IFN 特征，以鉴定在每个疾病的外周血和疾病组织中均显示 I 型 IFN 途径激活和一致性的亚群，并将该途径在 WB 中的激活与临床测量相关联。
在所有患者的 WB 中，确定了一组共同的 36 种 I 型 IFN 诱导转录本。在研究的五种疾病的亚组中观察到 I 型 IFN 途径的显著激活。SLE、PM 和 SSc 患者的 WB 基线疾病活动测量与 IFN 基因标志物相关，SLE 和 DM 患者的各种血清自身抗体水平也与该标志物相关。在 SLE、DM、PM 和 SSc 患者中，该标志物在疾病组织和 WB 之间也具有很好的相关性。
结果表明，I 型 IFN 途径在五种风湿性疾病的患者亚群中被激活，并提示这些亚群可能受益于抗 IFN 治疗。
