Interleukin-6 and Type I Interferon-Regulated Genes and Chemokines Mark Disease Activity in Dermatomyositis
Interleukin-6 and Type I Interferon-Regulated Genes and Chemokines Mark Disease Activity in Dermatomyositis
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DOI：
10.1002/art.24936
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发表时间：
2009-11-01
影响因子：
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通讯作者：
Reed, Ann M.
中科院分区：
文献类型：
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作者：
Bilgic, Hatice;Ytterberg, Steven R.;Reed, Ann M.
objective.在许多自身免疫性疾病中已经描述了全血I型干扰素（IFN）驱动的转录物和趋化因子的上调。IFN基因表达"特征"是皮肌炎（DM）患者的候选生物标志物。本研究旨在评估IFN依赖性外周血基因和趋化因子特征以及促炎细胞因子水平作为成人和青少年DM疾病活动性生物标志物的能力。从56例成人或青少年DM患者中获得外周血样本和临床数据。通过使用定量实时逆转录聚合酶链反应测定3种IFN调节基因（IFIT1、G1P2和IRF7）的表达水平，确定DM患者全血中的I型IFN基因特征。采用多重免疫测定法定量测定血清中4种I型IFN调节的趋化因子（IFN诱导的T细胞a趋化因子、IFN γ诱导的10-kd蛋白、单核细胞趋化蛋白1 [MCP-1]和MCP-2）水平以及其他促炎细胞因子（包括白细胞介素-6（IL-6））水平。DM疾病活动性与I型IFN基因特征（r = 0.41，P = 0.007）和I型IFN趋化因子特征（r = 0.61，P <0.0001）显著相关。血清IL-6水平与疾病活动度呈显著相关（r = 0.45，P = 0.001）。此外，DM患者血清IL-6水平与I型IFN基因标签（r = 0.47，P <0.01）和I型IFN趋化因子标签（r = 0.71，P <0.0001）均存在相关性。这些结果表明，血清IL-6的产生和I型IFN基因签名是成人和青少年DM疾病活动的候选生物标志物。IFN驱动的趋化因子和IL-6表达的共调节提示DM中存在一种新的致病联系。
Objective. Up-regulation of whole blood type I interferon (IFN)-driven transcripts and chemokines has been described in a number of autoimmune diseases. An IFN gene expression "signature" is a candidate biomarker in patients with dermatomyositis (DM). This study was performed to evaluate the capacity of IFN-dependent peripheral blood gene and chemokine signatures and levels of proinflammatory cytokines to serve as biomarkers for disease activity in adult and juvenile DM.Methods. Peripheral blood samples and clinical data were obtained from 56 patients with adult or juvenile DM. The type I IFN gene signature in the whole blood of patients with DM was defined by determining the expression levels of 3 IFN-regulated genes (IFIT1, G1P2, and IRF7) using quantitative real-time reverse transcription-polymerase chain reaction. Multiplexed immunoassays were used to quantify the serum levels of 4 type I IFN-regulated chemokines (IFN-inducible T cell a chemoattractant, IFN gamma-inducible 10-kd protein, monocyte chemotactic protein 1 [MCP-1], and MCP-2) and the serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6).Results. DM disease activity correlated significantly with the type I IFN gene signature (r = 0.41, P = 0.007) and with the type I IFN chemokine signature (r = 0.61, P < 0.0001). Furthermore, the serum levels of IL-6 were significantly correlated with disease activity (r = 0.45, P = 0.001). In addition, correlations between the serum levels of IL-6 and both the type I IFN gene signature (r = 0.47, P < 0.01) and the type I IFN chemokine signature (r = 0.71, P < 0.0001) were detected in patients with DM.Conclusion. These results suggest that serum IL-6 production and the type I IFN gene signature are candidate biomarkers for disease activity in adult and juvenile DM. Coregulation of the expression of IFN-driven chemokines and IL-6 suggests a novel pathogenic linkage in DM.